A Mixture of “Cheats” and “Co-Operators” Can Enable Maximal Group Benefit

It is commonly assumed that the world would be best off if everyone co-operates. Experimental and mathematical analysis of “co-operation” in yeast show why this isn't always the case

A Novel High-Affinity Sucrose Transporter Is Required for Virulence of the Plant Pathogen Ustilago maydis

A novel, high-affinity sucrose transporter identified in the plasma membrane of the plant pathogen Ustilago maydis is essential for fungal virulence and successful infection of maize

Contemporary management of primary parapharyngeal space tumors

The parapharyngeal space is a complex anatomical area. Primary parapharyngeal tumors are rare tumors and 80% of them are benign. A variety of tumor types can develop in this location; most common are salivary gland neoplasm and neurogenic tumors. The management of these tumors has improved greatly owing to the developments in imaging techniques, surgery, and radiotherapy. Most tumors can be removed with a low rate of complications and recurrence. The transcervical approach is the most frequently used. In some cases, minimally invasive approaches may be used alone or in combination with a limited transcervical route, allowing large tumors to be removed by reducing morbidity of expanded approaches. An adequate knowledge of the anatomy and a careful surgical plan is essential to tailor management according to the patient and the tumor. The purpose of the present review was to update current aspects of knowledge related to this more challenging area of tumor occurrence.Peer reviewe

Glycosylation of immunoglobulin G is regulated by a large network of genes pleiotropic with inflammatory diseases

Effector functions of immunoglobulin G (IgG) are regulated by the composition of a glycan moiety, thus affecting activity of the immune system. Aberrant glycosylation of IgG has been observed in many diseases, but little is understood about the underlying mechanisms. We performed a genome-wide association study of IgG N-glycosylation (N = 8090) and, using a data-driven network approach, suggested how associated loci form a functional network. We confirmed in vitro that knockdown of IKZF1 decreases the expression of fucosyltransferase FUT8, resulting in increased levels of fucosylated glycans, and suggest that RUNX1 and RUNX3, together with SMARCB1, regulate expression of glycosyltransferase MGAT3. We also show that variants affecting the expression of genes involved in the regulation of glycoenzymes colocalize with variants affecting risk for inflammatory diseases. This study provides new evidence that variation in key transcription factors coupled with regulatory variation in glycogenes modifies IgG glycosylation and has influence on inflammatory diseases.Molecular Epidemiolog

Cholangiocarcinoma

Exploratory laparotomy is frequently used to diagnose, treat, or palliate cholangiocarcinoma although surgery is rarely curative. In light of newly developed percutaneous and endoscopic approaches to diagnosis and therapy, we reviewed our experience with 35 cases of cholangiocarcinoma diagnosed and treated at the University of Michigan Medical Center from 1979 to 1984. Percutaneous transhepatic cholangiography (PTCA) was performed in 34 cases of which only four were resectable. All 22 patients who had preoperative cholangiograms suggesting unresectability had confirmation of this at surgery. Surgical palliation was accomplished with a combination of internal and percutaneous drainage in most cases. Angiographic, cytologic, and laboratory data are presented. PTCA accurately predicted unresectability of cholangiocarcinoma and is superior to angiography in this respect. In patients with cholangiocarcinoma, percutaneous and endoscopic approaches offer alternatives to surgery for diagnosis and palliation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44406/1/10620_2005_Article_BF01798361.pd

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

From birth to lying on- or under a supplemental heat source: How long does it take for half the litter to lie down and how long do they stay?

Piglets are susceptible to hypothermia because they lack hair and energy reserves, have a large surface area to body weight ratio, and have poor body thermostability. Different heat sources are used on farm, but it is not known how long it takes half a litter to locate it and lie down. The objectives of this study were to determine 1) how long it took for ≥ 50% of piglets to locate and lie on- or under the supplemental heat source for ≥ 5 min after the birth of the last-born pig and, 2) how long this cohort of piglets laid on- or under the heat source. A total of 12 sows were enrolled in the study (parity 1 = 4; 3 = 2; 4 = 2; 5 = 2; and 7 = 2). The stall containing one sow and her litter was the experimental unit. Two treatments were compared: 1) Baby Pig Heat Mat—Single 48 (MAT) and 2) Poly Heat Lamp (LAMP). Temperature was 32°C for both heat source treatments. Sow and litter video recordings occurred continually over a 24-h period on the day of farrowing. Two measures were determined 1) how long it took for ≥ 50% of piglets to locate and lie on- or under the supplemental heat source for ≥ 5 min after the birth of the last-born pig (h:min), and 2) how long this cohort of piglets laid on- or under the heat source (min:sec). Lying was defined as either sternal or lateral recumbency with ≥ 75% of the piglet’s body touching the heat mat or inside the lamp heat circle. Production records were used to verify farrowing date, total number of piglets born, and born alive. No cross fostering occurred during this study. All data will be presented descriptively. On average, sows assigned to the LAMP treatment took ~2 ½-h to farrow, and for sows assigned to the MAT ~3 ½-h, respectively. Piglets took between ~5-h (LAMP) and ~9-h (MAT) for ≥ 50% of piglets to locate and lie on- or under the supplemental heat source for ≥ 5 min after the birth of the last piglet. Cohort of piglets laid on- or under the heat source as follows, LAMP piglets spent ~29 mins lying and for MAT piglets ~42 mins, respectively. Average pre-weaning mortality was 11% (LAMP) and 18% (MAT). The MAT heat source used less energy than the LAMP (16 vs. 63 kWh) over the study duration. To the authors’ knowledge, this is the first published study using a continuous sampling method to precisely examine a new measure (time needed for ≥ 50% of piglets to locate and lie on- or under the supplemental heat source for ≥ 5 min after the birth of the last-born piglet) and to determine how long this cohort of piglets laid on- or under the heat source. Our findings show an immense range in locating and lying under- or on the heat source. Therefore, we suggest that caretakers should assist all piglets to locate the heat source after farrowing is complete to improve piglet livability.This article is published as Stambuk CR, Johnson AK, Lane KJ, Stalder KJ (2023) From birth to lying on- or under a supplemental heat source: How long does it take for half the litter to lie down and how long do they stay? PLoS ONE 18(12): e0294336. https://doi.org/10.1371/journal.pone.0294336. © 2023 Stambuk et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited