bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined Antihypertensive Therapies That Increase Expression of Cardioprotective Biomarkers Associated With the Renin–Angiotensin and Kallikrein–Kinin Systems
Authors: Lezama-Martinez Diego , Flores-Monroy Jazmin , Fonseca-Coronado Salvador , Hernandez-Campos Maria Elena , Valencia-Hernandez Ignacio , Martinez-Aguilar Luisa
Published: November 2018

Antihypertensive pharmacological treatments focus on the use of angiotensin-converting enzyme (ACE) inhibitors, AT1 receptor antagonists, and beta-blockers as single and combined treatments. The effect of single treatments on the mRNA expression of some components of the renin–angiotensin system has been studied, but not the effect of combined treatments. This study determined the expression of the AT1, AT2, B1, and B2 receptors and of the enzymes ACE and ACE2 in hypertensive rats treated with captopril–propranolol or losartan–propranolol. Methods: The mRNA expression of the receptors and enzymes was determined by reverse transcription-quantitative polymerase chain reaction in the aorta of spontaneously hypertensive rats under different treatments. Results: Rats under combined treatments showed a decrease in the expression of AT1 and ACE, and an increase in the expression of the B1 receptor (captopril + propranolol group: 0.43 ± 0.046, 2.243 ± 0.269, 3.356 ± 0.418; Group: losartan + propranolol: 0.727 ± 0.071, 0.852 ± 0.102, 1.277 ± 0.131 compared to the spontaneously hypertensive group: 1 ± 0.212, 1 ± 0.192, 1 ± 0.214). This decrease in the expression of ACE and AT1 suggests a reduction in the expression of Ang II that could be related to a lower response to this vasoconstrictor. An increase in the expression of B1 would improve vasodilation, which would be a beneficial effect of combined therapies for hypertension.
Late Phases of Cardioprotection During Remote Ischemic Preconditioning and Adenosine Preconditioning Involve Activation of Neurogenic Pathway
Authors: Singh Harinder , Kumar Manish , Singh Nirmal , Jaggi Amteshwar Singh
Published: November 2018

Background:

The role of the neurogenic pathway in early phases of cardioprotection during remote ischemic preconditioning (RIPC) and adenosine preconditioning is reported.

Aim:

This study was designed to explore the involvement of the neurogenic pathway in late phases of cardioprotection during RIPC and adenosine preconditioning.

Material and Methods:

Fifty-four Wistar rats were used and divided into 9 experimental groups. RIPC was induced by tying the blood pressure cuff around the hind limb and subjecting to 4 cycles of inflation and deflation of 5 minutes each. In early RIPC, the heart was isolated immediately after the last episode of RIPC, whereas in late RIPC, the heart was isolated 24 hours after the last cycle of RIPC. In a similar way, adenosine preconditioning was instituted in early and late phases by either isolating the heart 40 minutes or 24 hours after adenosine (4 mg/kg, intraperitoneally [i.p.]) administration. Isolated hearts were subjected to ischemia–reperfusion (I/R) injury on the Langendorff's system.

Results:

Both early and late phases of RIPC and adenosine preconditioning significantly abrogated I/R-induced myocardial injury in terms of decrease in the release of lactate dehydrogenase, creatine kinase, and decrease in infarct size. Pretreatment with hexamethonium, a ganglion blocker (20 mg/kg, i.p.), significantly abolished the cardioprotective effects of both early and late phases of RIPC and adenosine preconditioning.

Conclusion:

Apart from the involvement of the neurogenic pathway in the early phases, there is a critical role of the neurogenic pathway in the late phase of cardioprotection during RIPC and adenosine preconditioning.
Single Stage Repair of #30 Facial Cleft with Bone Morphogenic Protein
Authors: Sheckter Clifford C. , Mittermiller Paul , Hung Kay , Maan Zeshaan , Rochlin Danielle , Menard Robert M.
Published: November 2018

Tessier #30 clefts (median mandibular clefts) represent a spectrum of deformities ranging from a minor cleft in the lower lip to complete clefts of the mandible involving the tongue, lower lip, hyoid bone, thyroid cartilages, and manubrium. Various techniques have been used to address these problems; the most common procedure involving 2 stages: an initial correction of the soft tissue followed by closure of the mandibular cleft at a later date using bone grafting. This approach was subsequently reduced to a single operation, but still required harvesting of autologous bone graft. Here, we describe a modified single-stage operation using human recombinant bone morphogenic protein, avoiding bone graft harvest and allowing for simultaneous treatment of bone and soft tissue.
Small Growth in Child’s Mouth
Authors: Ivey Lauren A. , Moncrieff Norma , Jacob Sharon E.
Published: November 2018

Teledermatology is a term to describe the provision of dermatologic medical services through telecommunication technology. This is a teledermatology case of a child with a solitary papule on the gingival mucosa just inferior to the lower midline incisors.
Cost-effectiveness of a high-intensity rapid access outpatient stroke rehabilitation program
Authors: Tam Alan , Mac Stephen , Isaranuwatchai Wanrudee , Bayley Mark
Published: November 2018

A common strategy to improve cost-effectiveness in healthcare is to offer outpatient care instead of in-hospital care. Toronto Rehabilitation Institute developed an outpatient high-intensity fast-track (FT) stroke rehabilitation program aimed at discharging inpatient stroke rehabilitation patients earlier or bypassing inpatient rehabilitation altogether. This cost-effectiveness analysis compares FT rehabilitation within 1 week of discharge with no FT in a single healthcare payer system. Patient costs and outcomes over a 12-week time horizon were included. Using individual-level FT data from April 2015 to March 2016, incremental cost-effectiveness ratios (ICERs) (with 95% confidence interval) were estimated using regression. Subgroup analysis was completed for patients entering FT directly from inpatient rehabilitation and acute stroke care. Uncertainty was assessed using a cost-effectiveness acceptability curve with a range of willingness-to-pay values ($0–1000 per inpatient day saved). ICER (95% confidence interval) estimate for patients entering FT from inpatient rehabilitation was $404 ($270–620) per inpatient day saved. ICER estimate for direct from acute care admissions was $37 ($20–55) per day saved. At willingness-to-pay of $698 (cost of one alternate level of care day in acute care awaiting rehabilitation), the probability of FT being cost-effective was 99.2 and 100% for patients from inpatient rehabilitation and acute stroke care, respectively. From a single healthcare payer perspective, FT is a cost-effective method of providing appropriate rehabilitation intensity for stroke patients early on, and likely to provide savings to the healthcare system upstream through fewer days awaiting rehabilitation admission.
Tablet Computer as a Distraction Tool During Facial Laceration Repair
Authors: Bryl Amy W. , Bonsu Bema , Johnson Ariana L. , Pommert Kathleen B. J. , Hollenbach Kathryn A. , Kanegaye John T.
Published: November 2018

Objectives

Child life interventions reduce the anxiety of medical procedures but are not always available in emergency departments. In this study, we determined the effect of parent-directed tablet computer use without child life direction on patient anxiety and on parent and suturing clinician experience during pediatric facial laceration repair.

Methods

In a children's hospital emergency department, we enrolled children 2 to 12 years of age undergoing unsedated facial laceration repairs and randomized them to parent-directed tablet computer distraction or standard supportive care. We measured anxiety using the Observational Scale of Behavioral Distress—Revised (OSBD-R) for 5 procedure phases from videotaped laceration repairs. We compared OSBD-R scores for 5 phases and weighted averages between the tablet and standard care groups. Parents and suturing clinicians completed surveys about their experiences after the procedures.

Results

From April 2014 to July 2015, 77 patients (39 tablet, 38 standard) underwent repairs. Age, use of restraint, procedure duration, and number of sutures were similar between the 2 groups. The groups did not differ in procedure phase or weighted-average OSBD-R scores. Parents in the tablet group reported less personal anxiety compared with parents in the standard group (P = 0.01). In a post hoc subgroup analysis, subjects in the unrestrained tablet group had lower OSBD-R scores during the anesthetic injection phase than did subjects in the unrestrained standard group (P = 0.04). If restrained, subjects in the tablet group had higher OSBD-R scores during the anesthetic injection phase than did subjects in the standard group (P = 0.048).

Conclusions

Unrestrained children may benefit from parent-directed tablet computer distraction. Parents who operate the device are less anxious during their children's procedures.
A Comprehensive Pediatric Acute Sexual Assault Protocol
Authors: Kaplan Dana M. , Moore Jessica L. , Hirway Priyadarshini , Barron Christine E. , Goldberg Amy P.
Published: November 2018

Objective

Close medical follow-up after pediatric acute sexual assault is recommended and may mitigate adverse consequences and decrease long-term comorbidities. The objectives are to (1) examine adherence to a comprehensive outpatient medical follow-up protocol after evaluation in the emergency department in a pediatric population and (2) identify characteristics associated with patient adherence to inform the utilization of a medical follow-up protocol after pediatric acute sexual assault.

Methods

A retrospective medical record review was conducted of patients younger than 18 years presenting to the emergency department from January 1, 2010, to December 31, 2013, with a discharge diagnosis suggestive of sexual assault/abuse. We examined differences in demographics, assault characteristics, and medical/legal needs of patients who were evaluated in follow-up versus patients who were not.

Results

Of 182 patients, 60.4% completed follow-up appointments with the child protection center. Younger patients had follow-up rates higher than older patients (70.2% vs 50%; odds ratio [OR], 0.42). For patients where child protective services or law enforcement were called, follow-up rates were 74.2% and 64.7%, respectively (OR, 2.5; OR, 3.1). All patients with anogenital injuries on initial examination were seen in follow-up. The majority of patients who followed-up were accompanied by a caregiver/relative (95%).

Conclusions

(1) Caregivers should be integrated into the evaluation to facilitate compliance with follow-up; (2) child abuse specialists may be consulted to facilitate specific interventions and recommendations; (3) professionals should work as a multidisciplinary team; and (4) the patient's psychological status should be evaluated, and mental health interventions recommended.
Consensus Statement on Urgent Care Centers and Retail Clinics in Acute Care of Children
Authors: Saidinejad Mohsen , Paul Audrey , Gausche-Hill Marianne , Woolridge Dale , Heins Alan , Scott William Russell , Friesen Phillip , Rayburn David , Conners Gregory , Petrack Emory , Horeczko Timothy , Stoner Michael , Edgerton Elizabeth , Joseph Madeline
Published: November 2018

This article provides recommendations for pediatric readiness, scope of services, competencies, staffing, emergency preparedness, and transfer of care coordination for urgent care centers (UCCs) and retail clinics that provide pediatric care. It also provides general recommendations for the use of telemedicine in these establishments. With continuing increases in wait times and overcrowding in the nation's emergency departments and the mounting challenges in obtaining timely access to primary care providers, a new trend is gaining momentum for the treatment of minor illness and injuries in the form of UCCs and retail clinics. As pediatric visits to these establishments increase, considerations should be made for the type of injury or illnesses that can be safely treated, the required level training and credentials of personnel needed, the proper equipment and resources to specifically care for children, and procedures for safe transfer to a higher level of care, when needed. When used appropriately, UCCs and retail clinics can be valuable and convenient patient care resources.
Acute Flaccid Paralysis in an 11-Year-Old
Authors: Schwartz Lisa , Bishop Rebecca , Le Jacqueline , Hu Eugene , Kim Tommy
Published: November 2018

Rhabdomyolysis is a syndrome caused by injury to skeletal muscle and subsequent release of intracellular components into the systemic circulation. We report a case of rhabdomyolysis causing acute paralysis from underlying and unrecognized hypothyroidism in an 11-year-old girl. To date, publications of rhabdomyolysis secondary to hypothyroidism have been limited, especially in the pediatric population. Early intervention with intravenous fluids and levothyroxine led to resolution of our patient's symptoms and is overall important in preventing the serious sequela of rhabdomyolysis including renal failure, cardiac dysrhythmias, compartment syndrome, and disseminated intravascular coagulation.
Extended Patient Alone Time in Emergency Department Leads to Increased Risk of 30-Day Hospitalization
Authors: VanDeusen Adam J. , Pasupathy Kalyan S. , Huschka Todd R. , Heaton Heather A. , Hellmich Thomas R. , Sir Mustafa Y.
Published: November 2018

Objectives

This study was conducted to describe patients at risk for prolonged time alone in the emergency department (ED) and to determine the relationship between clinical outcomes, specifically 30-day hospitalization, and patient alone time (PAT) in the ED.

Methods

An observational cohort design was used to evaluate PAT and patient characteristics in the ED. The study was conducted in a tertiary academic ED that has both adult and pediatric ED facilities and of patients placed in an acute care room for treatment between May 1 and July 31, 2016, excluding behavioral health patients. Simple linear regression and t tests were used to evaluate the relationship between patient characteristics and PAT. Logistic regression was used to evaluate the relationship between 30-day hospitalization and PAT.

Results

Pediatric patients had the shortest total PAT compared with all older age groups (86.4 minutes versus 131 minutes, P < 0.001). Relationships were seen between PAT and patient characteristics, including age, geographic region, and the severity and complexity of the health condition. Controlling for Charlson comorbidity index and other potentially confounding variables, a logistic regression model showed that patients are more likely to be hospitalized within 30 days after their ED visit, with an odds ratio (95% confidence interval) of 1.056 (1.017–1.097) for each additional hour of PAT.

Conclusions

Patient alone time is not equal among all patient groups. Study results indicate that PAT is significantly associated with 30-day hospitalization. This conclusion indicates that PAT may affect patient outcomes and warrants further investigation.
The Ambulatory Version of the Safety Attitude Questionnaire: Psychometric Validation and Measurement Properties in Nigerian Clinical Setting
Authors: Ogaji Daprim Samuel , Emudiaga-Ohwerhi Mabel , Adesina Adedotun Daniel
Published: November 2018

Background

Understanding the safety culture of health care providers can help administrators improve patient safety. However, it is difficult to measure complex constructs such as safety culture without valid and reliable tools. This study determined the measurement properties of the ambulatory version of the safety attitude questionnaire (SAQ-AV) in the Nigerian clinical setting.

Methods

A multiphase, iterative research involving clinical staff in primary and tertiary level of care in South-south Nigeria. The phases included face and content validity by subject experts, pretesting with clinical staff and a field validation involving 812 clinical staff. The acceptability, reliability (internal consistency), and validity (face, content, and construct) of the SAQ-AV were determined. All quantitative analysis was conducted using the SPSS Version 22 statistical package with statistical significance set at a P value of less than 0.05.

Results

A response rate of 53.7% was obtained during the field validation study. The item nonresponse rates were less than 10%, whereas extremes of the response scale were frequently endorsed. The internal consistency of the scale was good (Cronbach’s α of 0.91 for entire scale and ranged from 0.62 to 0.76 among the different domains of the tool). Patient safety culture scores from primary and tertiary health care facilities assessed were significantly different.

Conclusions

The SAQ-AV is an acceptable, reliable, and valid tool for use in assessing patient safety culture in ambulatory settings in Nigeria. There is a need to determine its dimensionality and factor structure in future research.
Chyle Leak Following Autologous Breast Reconstruction
Authors: Long Samuel R. , Butterworth James A.
Published: November 2018

Background

While complications of deep inferior epigastric artery perforator flaps are known and well documented, a thorough literature review revealed no other reports of a patient developing a chyle leak following the use of the internal mammary vessels for recipient vessels in autologous breast reconstruction.

Case

A 55-year-old woman underwent free autologous breast reconstruction. She developed a chyle leak during the postoperative period. This was verified through a computed tomography scan and fluid analysis demonstrating a high triglyceride count and the presence of chylomicrons. The leak resolved with conservative measures including compression and a low-fat, high-protein diet.

Discussion

The presence of chyle leak following dissection of the internal mammary vessels is a unique complication of autologous breast reconstruction. There have been reports of lymph leaks following mastectomy, but these are mostly reported in the axilla. A history of radiation to the contralateral breast and aberrant anatomy may have contributed to the complication. Treatment of chyle leaks ranges from conservative management to the use of total parenteral nutrition and somatostatin analogs to surgical intervention.

Conclusion

While altering practice patterns based on a single case is not usually suggested, this complication does intimate that dealing with lymphatic vessels and lymph nodes in the chest should be done deliberately to prevent lymphatic leaks.
Determinants of Free Fasciocutaneous Flap Outcomes in Partial Hypopharyngeal Defects
Authors: Chen Ching-En , Wu Shang-Liang , Liao Wen-Chieh , Perng Cherng-Kang , Ma Hsu , Lin Chih-Hsun
Published: November 2018

Background

Most of the patients with hypopharyngeal cancer are still diagnosed with advanced stage, and total or partial pharyngectomy with free flap reconstruction is the mainstay of treatment. The aim of this study was to find out the possible risk factors related to surgical complications after free fasciocutaneous flap reconstruction for partial pharyngeal defect and its sequelae in the follow-up.

Patients and Methods

We retrospectively reviewed the charts of patients with advanced hypopharyngeal cancer who received free fasciocutaneous flaps for partial pharyngeal defects reconstruction. From 2005 to 2015, 79 free fasciocutaneous flaps (59 free fasciocutaneous flaps and 20 anterolateral thigh flaps) were performed in our department. The risk factors for free flap outcome and complications were evaluated with multivariant linear regression model.

Results

The mean age of patients was 60.8 years with male predominance. The mean follow-up duration was 39.6 months. Most of the cases (97.5%) were in stage III or IV. Patients with comorbidities showed significant correlation to flap failure (95% confidence interval [CI] = 0.038 to 0.264, P = 0.10). Anastomosis style (end-to-side vs end-to-end) was the only operation-related factors significantly related to flap failure rate (18.8% vs 3.2%, 95% CI = 0.031 to 0.32, P = 0.18). Flap size was significantly associated with fistula formation (95% CI = −0.005 to 0.000, P = 0.38).

Conclusions

In our experience, patients with comorbidities and end-to-side anastomosis illustrate significantly higher flap failure rate in free fasciocutaneous flap reconstruction of partial hypopharyngeal defect. Reconstruction with smaller flap size had higher possibility of fistula formation.
Oxygenated UW Solution Decreases ATP Decay and Improves Survival After Transplantation of DCD Liver Grafts
Authors: Martins Paulo N. , Berendsen Timothy A. , Yeh Heidi , Bruinsma Bote G. , Izamis Maria-Louisa , Op den Dries Sanna , Gillooly Andrew R. , Porte Robert , Yarmush Martin L. , Uygun Korkut , Markmann James F.
Published: November 2018

Background

Donation after circulatory death (DCD) liver grafts are known to be predisposed to primary nonfunction and ischemic cholangiopathy. Many DCD grafts are discarded because of older donor age or long warm ischemia times. Thus, it is critical to improve the quality of DCD liver grafts. Here, we have tested whether an enriched oxygen carrier added to the preservation solution can prolong graft survival and reduce biliary damage.

Methods

We assessed the adenosine triphosphate (ATP) content decay of mouse liver grafts after cold ischemia, warm ischemia, and combined warm+cold ischemia. In addition, we used a rat model of liver transplantation to compare survival of DCD grafts preserved in high-oxygen solution (preoxygenated perfluorocarbon [PFC] + University of Wisconsin [UW] solution) versus lower oxygen solution (preoxygenated UW solution).

Results

Adenosine triphosphate levels under UW preservation fall to less than 10% after 30 minutes of warm ischemia. Preoxygenated UW solution with PFC reached a significantly higher PaO2. After 45 minutes of warm ischemia in oxygenated UW + PFC solution, grafts showed 63% higher levels of ATP (P = 0.011). In addition, this was associated with better preservation of morphology when compared to grafts stored in standard UW solution. Animals that received DCD grafts preserved in higher oxygenation solution showed improved survival: 4 out of 6 animals survived long-term whereas all control group animals died within 24 hours.

Conclusions

The additional oxygen provided by PFC during static cold preservation of DCD livers can better sustain ATP levels, and thereby reduce the severity of ischemic tissue damage. PFC-based preservation solution extends the tolerance to warm ischemia, and may reduce the rate of ischemic cholangiopathy.
Spectral Content of Electroencephalographic Burst-Suppression Patterns May Reflect Neuronal Recovery in Comatose Post-Cardiac Arrest Patients
Authors: Sekar Krithiga , Schiff Nicholas D. , Labar Douglas , Forgacs Peter B.
Published: November 2018

Purpose:

To assess the potential biologic significance of variations in burst-suppression patterns (BSPs) after cardiac arrest in relation to recovery of consciousness. In the context of recent theoretical models of BSP, bursting frequency may be representative of underlying network dynamics; discontinuous activation of membrane potential during impaired cellular energetics may promote neuronal rescue.

Methods:

We reviewed a database of 73 comatose post-cardiac arrest patients who underwent therapeutic hypothermia to assess for the presence of BSP and clinical outcomes. In a subsample of patients with BSP (n = 14), spectral content of burst and suppression periods were quantified using multitaper method.

Results:

Burst-suppression pattern was seen in 45/73 (61%) patients. Comparable numbers of patients with (31.1%) and without (35.7%) BSP regained consciousness by the time of hospital discharge. In addition, in two unique cases, BSP initially resolved and then spontaneously reemerged after completion of therapeutic hypothermia and cessation of sedative medications. Both patients recovered consciousness. Spectral analysis of bursts in all patients regaining consciousness (n = 6) showed a prominent theta frequency (5–7 Hz) feature, but not in age-matched patients with induced BSP who did not recover consciousness (n = 8).

Conclusions:

The prognostic implications of BSP after hypoxic brain injury may vary based on the intrinsic properties of the underlying brain state itself. The presence of theta activity within bursts may index potential viability of neuronal networks underlying recovery of consciousness; emergence of spontaneous BSP in some cases may indicate an innate neuroprotective mechanism. This study highlights the need for better characterization of various BSP patterns after cardiac arrest.
Probing layered arc crust in the Lesser Antilles using receiver functions
Authors: Schlaphorst David , Melekhova Elena , Kendall J-Michael , Blundy Jon , Latchman Joan L.
Published: November 2018

Oceanic arcs can provide insight into the processes of crustal growth and crustal structure. In this work, changes in crustal thickness and composition along the Lesser Antilles Arc (LAA) are analysed at 10 islands using receiver function (RF) inversions that combine seismological data with v
P
/v
S
ratios estimated based on crustal lithology. We collected seismic data from various regional networks to ensure station coverage for every major island in the LAA from Saba in the north to Grenada in the south. RFs show the subsurface response of an incoming signal assuming horizontal layering, where phase conversions highlight discontinuities beneath a station. In most regions of the Earth, the Mohorovičić discontinuity (Moho) is seismically stronger than other crustal discontinuities. However, in the LAA we observe an unusually strong along-arc variation in depth of the strongest discontinuity, which is difficult to explain by variations in crustal thickness. Instead, these results suggest that in layered crust, especially where other discontinuities have a stronger seismic contrast than the Moho, H–
k
stacking results can be easily misinterpreted. To circumvent this problem, an inversion modelling approach is introduced to investigate the crustal structure in more detail by building a one-dimensional velocity–depth profile for each island. Using this method, it is possible to identify any mid-crustal discontinuity in addition to the Moho. Our results show a mid-crustal discontinuity at about 10–25 km depth along the arc, with slightly deeper values in the north (Montserrat to Saba). In general, the depth of the Moho shows the same pattern with values of around 25 km (Grenada) to 35 km in the north. The results suggest differences in magmatic H
2
O content and differentiation history of each island.
Acetophenone Mannich bases: study of ionic liquid catalysed synthesis and antioxidative potential of products
Authors: Petrović Vladimir P. , Simijonović Dušica , Milovanović Vesna M. , Petrović Zorica D.
Published: November 2018

Three-component Mannich reaction of acetophenone or 4-iodoacetophenone with a variety of substituted anilines and benzaldehyde, catalysed with diethanolammonium chloroacetate, was performed under mild conditions. Mannich bases (
MBs
), of which five are new, were obtained in good to excellent yields. All compounds were characterized using elemental analysis, NMR and IR. In addition, detailed experimental and simulated UV–Vis spectral characterization of these compounds is presented here for the first time.
In vitro
antioxidative potential of synthetized
MBs
was evaluated using 2,2-diphenyl-1-picryl-hydrazyl radical and density functional theory (DFT) thermodynamical study. It was shown that compounds with anisidine moiety express moderate antioxidative activity. Mechanism of the organocatalysed Mannich reaction was thoroughly inspected by means of DFT. The reaction undergoes the hydrogen bonding-assisted mechanism. Moreover, the proposed rate determining step of the overall reaction is water elimination in the process of iminium ion formation. To the extent of our knowledge, this is the first detailed report on the influence of this type of catalyst on the formation of iminium ion, as a crucial intermediate for the whole reaction.
Neonatal mice exposed to a high-fat diet
in utero
influence the behaviour of their nursing dam
Authors: Baptissart Marine , Lamb Harold E. , To Kimberly , Bradish Christine , Tehrani Jesse , Reif David , Cowley Michael
Published: November 2018

The behaviour of a nursing dam influences the development, physiology, and behaviour of her offspring. Maternal behaviours can be modulated both by environmental factors, including diet, and by physical or behavioural characteristics of the offspring. In most studies of the effects of the environment on maternal behaviour, F
0
dams nurse their own F
1
offspring. Because the F
1
are indirectly exposed to the environmental stressor
in utero
in these studies, it is not possible to differentiate between effects on maternal behaviour from direct exposure of the dam and those mediated by changes in the F
1
as a consequence of
in utero
exposure. In this study, we used a mouse model of high-fat (HF) diet feeding, which has been shown to influence maternal behaviours, combined with cross-fostering to discriminate between these effects. We tested whether the diet of the F
0
dam or the exposure experienced by the F
1
pups
in utero
is the most significant predictor of maternal behaviour. Neither factor significantly influenced pup retrieval behaviours. However, strikingly, F
1
in utero
exposure was a significant predictor of maternal behaviour in the 15 min immediately following pup retrieval while F
0
diet had no discernable effect. Our findings suggest that
in utero
exposure to HF diet programmes physiological changes in the offspring which influence the maternal behaviours of their dam after birth.
Carbon limitation of lake productivity
Authors: Kragh Theis , Sand-Jensen Kaj
Published: November 2018

Phytoplankton productivity in lakes controls the rate of synthesis of organic matter that drives energy flow through the food webs and regulates the transparency and oxygen conditions in the water. Limitation of phytoplankton productivity and biomass by nutrients and light availability is an established paradigm for lake ecosystems, whereas invasion of atmospheric CO2has been assumed to cover the high demands of dissolved inorganic carbon (DIC) during intense organic productivity. We challenge this paradigm, and show up to a 5-fold stimulation of phytoplankton productivity and biomass in outdoor mesocosms enriched with DIC, compared to mesocosms with lower DIC concentrations. High DIC supported phytoplankton productivity by direct algal uptake of bicarbonate, through the release of CO2coupled to calcification and by inducing high pH that greatly enhances atmospheric CO2invasion. Comparisons of 204 natural Danish lakes supported mesocosm experiments showing higher phytoplankton biomass and pH levels in hard water than soft water lakes for the same nutrient and light availabilities. The most productive lakes are nutrient-rich, hard water lakes that attain surface pHs of 10–11 and chemically enhance atmospheric CO2uptake 10–15-fold. Our results will help understand natural variations of lake productivity along gradients in nutrients, DIC and pH.
The hidden cost of sexually selected traits: the metabolic expense of maintaining a sexually selected weapon
Authors: Somjee Ummat , Woods H. Arthur , Duell Meghan , Miller Christine W.
Published: November 2018

Sexually selected weapons are among the most exaggerated traits in nature. Sexual selection theory frequently assumes a high cost of this exaggeration; yet, those costs are rarely measured. We know very little about the energetic resources required to maintain these traits at rest and the difference in energetic costs for the largest individuals relative to the smallest individuals. Knowledge in this area is crucial; resting metabolic rate can account for 30–40% of daily energy expenditure in wild animals. Here, we capitalized on the phenomenon of autotomy to take a unique look at weapon maintenance costs. UsingLeptoscelis tricolor(Hemiptera: Coreidae), we measured CO2production rates before and after a weapon was shed. Males in this insect species use enlarged hind femora as weapons in male–male combat, and yet can shed them readily, without regeneration, upon entrapment. We found that metabolic rate decreased by an average of 23.5% in males after leg loss and by 7.9% in females. Notably, larger males had less of a drop in metabolic rate per gram of weapon lost. Our findings suggest that sexually selected weapons contribute to a large portion of resting metabolic rate in males, but these costs do not scale in direct proportion to size; larger males can have larger weapons for a reduced metabolic cost. These energetic maintenance costs may be integral to the evolution of the allometries of sexually selected weapons, and yet they remain largely unexplored.
Exploring mechanisms and origins of reduced dispersal in island Komodo dragons
Authors: Jessop Tim S. , Ariefiandy Achmad , Purwandana Deni , Ciofi Claudio , Imansyah Jeri , Benu Yunias Jackson , Fordham Damien A. , Forsyth David M. , Mulder Raoul A. , Phillips Benjamin L.
Published: November 2018

Loss of dispersal typifies island biotas, but the selective processes driving this phenomenon remain contentious. This is because selection via, both indirect (e.g. relaxed selection or island syndromes) and direct (e.g. natural selection or spatial sorting) processes may be involved, and no study has yet convincingly distinguished between these alternatives. Here, we combined observational and experimental analyses of an island lizard, the Komodo dragon (Varanus komodoensis, the world's largest lizard), to provide evidence for the actions of multiple processes that could contribute to island dispersal loss. In the Komodo dragon, concordant results from telemetry, simulations, experimental translocations, mark-recapture, and gene flow studies indicated that despite impressive physical and sensory capabilities for long-distance movement, Komodo dragons exhibited near complete dispersal restriction: individuals rarely moved beyond the valleys they were born/captured in. Importantly, lizard site-fidelity was insensitive to common agents of dispersal evolution (i.e. indices of risk for inbreeding, kin and intraspecific competition, and low habitat quality) that consequently reduced survival of resident individuals. We suggest that direct selection restricts movement capacity (e.g. via benefits of spatial philopatry and increased costs of dispersal) alongside use of dispersal-compensating traits (e.g. intraspecific niche partitioning) to constrain dispersal in island species.
Microbial-tubeworm associations in a 440 million year old hydrothermal vent community
Authors: Georgieva Magdalena N. , Little Crispin T. S. , Bailey Russell J. , Ball Alexander D. , Glover Adrian G.
Published: November 2018

Microorganisms are the chief primary producers within present-day deep-sea hydrothermal vent ecosystems, and play a fundamental role in shaping the ecology of these environments. However, very little is known about the microbes that occurred within, and structured, ancient vent communities. The evolutionary history, diversity and the nature of interactions between ancient vent microorganisms and hydrothermal vent animals are largely undetermined. The oldest known hydrothermal vent community that includes metazoans is preserved within the Ordovician to early Silurian Yaman Kasy massive sulfide deposit, Ural Mountains, Russia. This deposit contains two types of tube fossil attributed to annelid worms. A re-examination of these fossils using a range of microscopy, chemical analysis and nano-tomography techniques reveals the preservation of filamentous microorganisms intimately associated with the tubes. The microfossils bear a strong resemblance to modern hydrothermal vent microbial filaments, including those preserved within the mineralized tubes of the extant vent polychaete genus
Alvinella
. The Yaman Kasy fossil filaments represent the oldest animal–microbial associations preserved within an ancient hydrothermal vent environment. They allude to a diverse microbial community, and also demonstrate that remarkable fine-scale microbial preservation can also be observed in ancient vent deposits, suggesting the possible existence of similar exceptionally preserved microfossils in even older vent environments.
Adaptation, speciation and extinction in the Anthropocene
Authors: Otto Sarah P.
Published: November 2018

Humans have dramatically altered the planet over the course of a century, from the acidity of our oceans to the fragmentation of our landscapes and the temperature of our climate. Species find themselves in novel environments, within communities assembled from never before encountered mixtures of invasives and natives. The speed with which the biotic and abiotic environment of species has changed has already altered the evolutionary trajectory of species, a trend that promises to escalate. In this article, I reflect upon this altered course of evolution. Human activities have reshaped selection pressures, favouring individuals that better survive in our built landscapes, that avoid our hunting and fishing, and that best tolerate the species that we have introduced. Human-altered selection pressures have also modified how organisms live and move through the landscape, and even the nature of reproduction and genome structure. Humans are also shaping selection pressures at the species level, and I discuss how species traits are affecting both extinction and speciation rates in the Anthropocene.
Statistically consistent divide-and-conquer pipelines for phylogeny estimation using NJMerge
Authors: Molloy Erin K. , Warnow Tandy
Published: November 2018

Background

Divide-and-conquer methods, which divide the species set into overlapping subsets, construct a tree on each subset, and then combine the subset trees using a supertree method, provide a key algorithmic framework for boosting the scalability of phylogeny estimation methods to large datasets. Yet the use of supertree methods, which typically attempt to solve NP-hard optimization problems, limits the scalability of such approaches.

Results

In this paper, we introduce a divide-and-conquer approach that does not require supertree estimation: we divide the species set into pairwise disjoint subsets, construct a tree on each subset using a base method, and then combine the subset trees using a distance matrix. For this merger step, we present a new method, called NJMerge, which is a polynomial-time extension of Neighbor Joining (NJ); thus, NJMerge can be viewed either as a method for improving traditional NJ or as a method for scaling the base method to larger datasets. We prove that NJMerge can be used to create divide-and-conquer pipelines that are statistically consistent under some models of evolution. We also report the results of an extensive simulation study evaluating NJMerge on multi-locus datasets with up to 1000 species. We found that NJMerge sometimes improved the accuracy of traditional NJ and substantially reduced the running time of three popular species tree methods (ASTRAL-III, SVDquartets, and “concatenation” using RAxML) without sacrificing accuracy. Finally, although NJMerge can fail to return a tree, in our experiments, NJMerge failed on only 11 out of 2560 test cases.

Conclusions

Theoretical and empirical results suggest that NJMerge is a valuable technique for large-scale phylogeny estimation, especially when computational resources are limited. NJMerge is freely available on Github (http://github.com/ekmolloy/njmerge).
A mathematical framework for modelling the metastatic spread of cancer
Authors: Franßen Linnéa C , Lorenzi Tommaso , Burgess Andrew EF , Chaplain Mark AJ
Published: November 2018

Cancer is a complex disease that starts with mutations of key genes in one cell or a small group of cells at a primary site in the body. If these cancer cells continue to grow successfully and, at some later stage, invade the surrounding tissue and acquire a vascular network (tumour-induced angiogenesis), they can spread to distant secondary sites in the body. This process, known asmetastatic spread, is responsible for around 90% of deaths from cancer and is one of the so-calledhallmarks of cancer.

To shed light on the metastatic process, we present a mathematical modelling framework that captures for the first time the interconnected processes of invasion and metastatic spread of individual cancer cells in a spatially explicit manner — a multi-grid, hybrid, individual-based approach. This framework accounts for the spatio-temporal evolution of mesenchymal- and epithelial-like cancer cells, as well as MT1-MMP and MMP-2 dynamics, and interactions with the extracellular matrix.

Using computational simulations, we demonstrate that our model captures all the key steps of the invasion-metastasis cascade, i.e. invasion by both heterogeneous cancer cell clusters and by single mesenchymal-like cancer cells; intravasation of these clusters and single cells both via active mechanisms mediated by matrix degrading enzymes (MDEs) and via passive shedding; circulation of cancer cell clusters and single cancer cells in the vasculature with the associated risk of cell death and disaggregation of clusters; extravasation of clusters and single cells; and metastatic growth at distant secondary sites in the body. By faithfully reproducing experimental results, our simulations support the evidence-based hypothesis that the membrane-bound MT1-MMP is the main driver of invasive spread rather than diffusible MDEs like MMP-2.
High Resolution Comparison of Cancer-Related Developmental Processes Using Trajectory Alignment
Authors: Alpert Ayelet , Starosvetsky Elina , Hayun Michal , Ofran Yishai , Shen-Orr Shai S.
Published: November 2018

Abnormal differentiation is a key feature of cancer, yet currently there is no framework that enables a comparative analysis of differentiation processes across patients while preserving their individual-level resolution. Here, we present devMap, an algorithm that uses high-dimensional trajectory alignment to anchor cancer-related developmental processes to a common backbone process, thus allowing for their systematic comparison. We applied devMap to bone marrow samples from healthy individuals and AML patients profiled by single-cell mass-cytometry at cancer diagnosis and following treatment. devMap standardization enabled us to infer the developmental status of the AML samples and characterize its evolution following treatment and in relapse. Application of devMap on an external dataset of AML bone marrow samples revealed conserved patterns of developmental signaling responses in AML that were obscured by traditional methodologies for developmental inference.
LINGO3 interacts with Trefoil factor 2 to enforce mucosal barrier integrity and drive tissue repair during colitis
Authors: Zullo Kelly M. , Ji Yingbiao , Wei Yun , Herbine Karl , Maloney Nicole , Cohen Rachel , Pastore Christopher , Samsouk Ma , Srivatsa Sriram , Hung Li Yin , Kohanski Michael H. , Cohen Noam A. , Herbert De’Broski R.
Published: November 2018

Mucosal epithelia are constantly exposed to damaging stimuli from mechanical, chemical, or biologic entities, and depend on rapid repair mechanisms to maintain tissue homeostasis and immunological quiescence. The reparative cytokine Trefoil factor 2 (TFF2) serves to enforce mucosal barrier integrity, but whether TFF2 receptor(s) exist is controversial. Herein, we demonstrate leucine rich repeat and immunoglobulin like domain containing nogo receptor interacting protein 3 (LINGO3) is a necessary transmembrane component for TFF2-mediated ERK signaling, proliferation, and recovery of trans-epithelial resistance of primary epithelia during wound healing. Human respiratory and intestinal epithelia express LINGO3 and mice lacking Lingo3 have impaired intestinal barrier function and fail to recover from DSS-induced colitis. Compared to wild-type controls, LINGO3 deficiency impairs both crypt regeneration and expression of the intestinal stem cell marker Lgr5. Importantly, Lingo3-/- mice display a phenotype similar to that previously reported for Tff2 deficiency, with increased paracellular permeability, and significant accumulation of mucosal CD4+ TH1 cells expressing IFNγ+ TNF+ even under steady-state conditions. Combined, these data reveal a previously unrecognized role for LINGO3 as a putative TFF2 receptor that regulates mucosal barrier integrity and GI inflammation.

Significance

Intestinal epithelial cells (IEC) are necessary for maintenance of homeostasis, resistance to infectious organisms, and overall organismal health. When injured the IEC and the underlying stroma and progenitor cell pool undergo restitutive and regenerative processes driven by the reparative cytokine Trefoil factor 2 (TFF2). This report identifies a novel receptor component for TFF2 signaling expressed on both human and mouse epithelial cells that is necessary for barrier integrity at the steady state and during colitic disease. The discovery of a novel TFF2-LINGO3 axis sheds new light on the processes controlling tissue repair, restitution, and regeneration at the mucosal interface.
TFF3 is a ligand for LINGO2 that de-represses EGFR to control disease outcome during colitis and gastrointestinal nematode infection
Authors: Ji Yingbiao , Wei Yun , Park JoonHyung , Hung Li Yin , Young Tanner , Herbine Karl , Oniskey Taylor , Pastore Christopher , Nieves Wildaliz , Somsouk Ma , Herbert De’Broski R.
Published: November 2018

Intestinal epithelial cells (IEC) comprise diverse lineages that serve distinct roles necessary for regulation of nutrient absorption, regeneration, immunity, and homeostasis1,2. Goblet cells secrete Trefoil factor 3 (TFF3) to maintain mucus viscosity and drive mucosal healing by inhibiting cell death and influencing tight junction protein expression3. However, whether TFF3 signaling relies upon conventional ligand-receptor interactions has been unclear for decades. This study demonstrates that the orphan transmembrane protein leucine rich repeat receptor and nogo-interacting protein 2 (LINGO2) immunoprecipitates with TFF3, that LINGO2 and TFF3 co-localize at the IEC cell surface, and that TFF3/LINGO2 interactions block IEC apoptosis. Loss of function studies show that TFF3-driven STAT3 and EGFR activation are both LINGO2 dependent. Importantly, we demonstrate that TFF3 disrupts LINGO2/EGFR interactions that normally restrict EGFR activity, resulting in enhanced EGFR signaling. Excessive EGFR activation in Lingo2 gene deficient mice exacerbates colitic disease and accelerates host resistance to parasitic nematodes, whereas TFF3 deficiency results in host susceptibility. Thus, our data demonstrating that TFF3 functions through a previously unrecognized ligand-receptor interaction with LINGO2 to de-repress LINGO2-dependent inhibition of EGFR activation provides a novel conceptual framework explaining how TFF3-mediates mucosal wound healing through enhanced activation of the EGFR pathway.