Evolutionarily divergent mTOR remodels translatome for tissue regeneration.

An outstanding mystery in biology is why some species, such as the axolotl, can regenerate tissues whereas mammals cannot. Here, we demonstrate that rapid activation of protein synthesis is a unique feature of the injury response critical for limb regeneration in the axolotl (Ambystoma mexicanum). By applying polysome sequencing, we identify hundreds of transcripts, including antioxidants and ribosome components that are selectively activated at the level of translation from pre-existing messenger RNAs in response to injury.

Acoustically Detonated Microbubbles Coupled with Low Frequency Insonation: Multiparameter Evaluation of Low Energy Mechanical Ablation.

Noninvasive ultrasound surgery can be achieved using focused ultrasound to locally affect the targeted site without damaging intervening tissues. Mechanical ablation and histotripsy use short and intense acoustic pulses to destroy the tissue via a purely mechanical effect. Here, we show that coupled with low-frequency excitation, targeted microbubbles can serve as mechanical therapeutic warheads that trigger potent mechanical effects in tumors using focused ultrasound.

A p53-dependent translational program directs tissue-selective phenotypes in a model of ribosomopathies.

In ribosomopathies, perturbed expression of ribosome components leads to tissue-specific phenotypes. What accounts for such tissue-selective manifestations as a result of mutations in the ribosome, a ubiquitous cellular machine, has remained a mystery. Combining mouse genetics and in vivo ribosome profiling, we observe limb-patterning phenotypes in ribosomal protein (RP) haploinsufficient embryos, and we uncover selective translational changes of transcripts that controlling limb development.

CRISPR/Cas9 mutagenesis reveals a role for ABCB1 in gut immune responses to Vibrio diazotrophicus in sea urchin larvae.

The ABC transporter ABCB1 plays an important role in the disposition of xenobiotics. Embryos of most species express high levels of this transporter in early development as a protective mechanism, but its native substrates are not known. Here, we used larvae of the sea urchin Strongylocentrotus purpuratus to characterize the early life expression and role of Sp-ABCB1a, a homolog of ABCB1.

Optogenetic manipulation of cellular communication using engineered myosin motors.

Cells achieve highly efficient and accurate communication through cellular projections such as neurites and filopodia, yet there is a lack of genetically encoded tools that can selectively manipulate their composition and dynamics. Here, we present a versatile optogenetic toolbox of artificial multi-headed myosin motors that can move bidirectionally within long cellular extensions and allow for the selective transport of GFP-tagged cargo with light. Utilizing these engineered motors, we could transport bulky transmembrane receptors and organelles as well as actin remodellers to control the dynamics of both filopodia and neurites.

Immediate Sequential Bilateral Vitreoretinal Surgery: Descriptive Case Series and Literature Review.

Background And Objective: Bilateral vision-threatening disease necessitating urgent surgery in both eyes is challenging in vitreoretinal disorders, where surgeries are often longer and higher risk than in other ocular disorders. The authors present a case series of patients undergoing immediate sequential bilateral vitreoretinal surgery (ISBVS) on the same day.

Patients And Methods: Retrospective case series and literature review.

The painted sea urchin, Lytechinus pictus, as a genetically-enabled developmental model.

Although sea urchins are one of the oldest and most widely used marine model systems, few species have been routinely kept in culture through multiple generations. The workhorse of the field is the purple urchin Strongylocentrotus purpuratus. However, one disadvantage of S.

Acute otitis media in infants younger than two months of age: Epidemiologic and microbiologic characteristics in the era of pneumococcal conjugate vaccines.

Objectives: To evaluate the epidemiology, microbiology, Streptococcus pneumoniae serotypes distribution and serious bacterial infections (SBIs) occurrence in infants <2 months of age with tympanocentesis-documented acute otitis media (AOM), before and after the introduction of pneumococcal conjugate vaccines (PCVs).

Methods: The medical records of all hospitalized infants with AOM who underwent tympanocentesis during 2005-2014 were reviewed.

Results: Of the 303 infants with AOM who were diagnosed by an ENT specialist, 182 underwent tympanocentesis, 92 during 2005-2009 (prevaccine period) and 90 during 2010-2014 (postvaccine period).

Learning and memory are impaired in the object recognition task during metestrus/diestrus and after sleep deprivation.

Females are an under-represented research model and the mechanisms through which sleep loss impairs cognition are not clear. Since levels of reproductive hormones and the estrous cycle are sensitive to sleep loss and necessary for learning and memory, we hypothesized that sleep deprivation impacts learning and memory in female mice by interfering with the estrous cycle. We used the object recognition task to assess learning and memory in female mice during separate phases of the estrous cycle and after sleep loss.

On Context and Meaning in Pocock's , and on Gibbon's "Protestantism" in His Chapters on Religion.

Rosenblatt questions whether Pocock's Barbarism and Religion, though enormously learned and rich, in fact accomplishes Pocock's stated aims. In other words, does the context presented help to explain the intended meaning and significance of Gibbon's Decline and Fall? She asks whether Pocock's methodology, indebted to the Cambridge School, is consistent and serviceable and challenges his claim that Gibbon should be seen as a member of the "Protestant Enlightenment."

Control lymphocyte subsets: can one country's values serve for another's?

Lymphocyte subsets can be affected by host and environmental factors, yet direct comparisons of their patterns across continents are lacking. This work compares proportions and counts of lymphocyte subsets between healthy children from Thailand, Malawi and the USA. We analyzed subsets of 1,399 healthy children aged between 0 and 15 years: 281 Thai, 397 Malawian and 721American children.

Gene therapy for adenosine deaminase-deficient severe combined immune deficiency: clinical comparison of retroviral vectors and treatment plans.

We conducted a gene therapy trial in 10 patients with adenosine deaminase (ADA)-deficient severe combined immunodeficiency using 2 slightly different retroviral vectors for the transduction of patients' bone marrow CD34(+) cells. Four subjects were treated without pretransplantation cytoreduction and remained on ADA enzyme-replacement therapy (ERT) throughout the procedure. Only transient (months), low-level (< 0.

Immunogenicity, immunologic memory, and safety following measles revaccination in HIV-infected children receiving highly active antiretroviral therapy.

Background: Response rates and immunologic memory following measles vaccination are reduced in human immunodeficiency virus (HIV)-infected children in the absence of highly active antiretroviral therapy (HAART).

Methods: HIV-infected children 2 to <19 years old receiving HAART and with HIV loads <30,000 copies/mL, CD4% ≥15, and ≥1 prior measles-mumps-rubella vaccination (MMR) were given another MMR. Measles antibody concentrations before and 8, 32, and 80 weeks postvaccination were determined by plaque reduction neutralization (PRN).

Excellent survival after sibling or unrelated donor stem cell transplantation for chronic granulomatous disease.

Background: Matched related donor (MRD) hematopoietic stem cell transplantation (HSCT) is a successful treatment for chronic granulomatous disease (CGD), but the safety and efficacy of HSCT from unrelated donors is less certain.

Objective: We evaluated the outcomes and overall survival in patients with CGD after HSCT.

Methods: We report the outcomes for 11 children undergoing HSCT from an MRD (n = 4) or an HLA-matched unrelated donor (MUD) (n = 7); 9 children were boys, and the median age was 3.

Vaccine-acquired rotavirus in infants with severe combined immunodeficiency.

Live pentavalent human-bovine reassortant rotavirus vaccine is recommended in the United States for routine immunization of infants. We describe three infants, two with failure to thrive, who had dehydration and diarrhea within 1 month after their first or second rotavirus immunization and subsequently received a diagnosis of severe combined immunodeficiency. Rotavirus was detected, by means of reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay, in stool specimens obtained from all three infants, and gene-sequence analysis revealed the presence of vaccine rotavirus.

Outcomes of patients with severe combined immunodeficiency treated with hematopoietic stem cell transplantation with and without preconditioning.

Background: The effect of pretransplantation conditioning on the long-term outcomes of patients receiving hematopoietic stem cell transplantation for severe combined immunodeficiency (SCID) has not been completely determined.

Objective: We sought to assess the outcomes of 23 mostly conditioned patients with SCID and compare their outcomes with those of 25 previously reported nonconditioned patients with SCID who underwent transplantation.

Methods: In the present study we reviewed the medical records of these 23 consecutive, mostly conditioned patients with SCID who underwent transplantation between 1998 and 2007.

Hemophagocytic lymphohistiocytosis in a patient with x-linked lymphoproliferative disease.

X-linked lymphoproliferative disease (XLP) is a primary immunodeficiency affecting approximately 1 to 3 per million live male births. Patients are generally healthy until facing a viral infection such as Epstein-Barr Virus and then may develop fulminant infectious mononucleosis and die. XLP patients are also at increased risk of hemophagocytic lymphohistiocytosis (HLH), which may be triggered by assorted viruses.

Immunogenicity and immunologic memory after hepatitis B virus booster vaccination in HIV-infected children receiving highly active antiretroviral therapy.

Background: Hepatitis B virus (HBV) is an important cause of comorbidity in human immunodeficiency virus (HIV)-infected individuals. The immunogenicity of HBV vaccination in children receiving highly active antiretroviral therapy (HAART) was investigated.

Methods: HIV-infected children receiving HAART who had low to moderate HIV loads and who had previously received 3 doses of HBV vaccine were given an HBV vaccine booster.

Long-term outcomes of nonconditioned patients with severe combined immunodeficiency transplanted with HLA-identical or haploidentical bone marrow depleted of T cells with anti-CD6 mAb.

Background: Between 1981 and 1995, 20 children with severe combined immunodeficiency (SCID; median age at transplant, 6.5 [range, 0.5-145] mo, 12 with serious infection) were treated with haploidentical T cell-depleted (anti-CD6 antibody) bone marrow (median number of 5.

Successful treatment of stem cell graft failure in pediatric patients using a submyeloablative regimen of campath-1H and fludarabine.

Graft failure is a significant cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). We used a nonmyeloablative conditioning regimen consisting of the lympho-depleting humanized CD52-antibody Campath-1H and fludarabine to rescue 12 consecutive children age 9 months to 17 years with engraftment failure after initial myeloablative HSCT. Primary diagnoses included lymphohematologic malignancies (n=6), severe combined immunodeficiency syndrome (SCID) (n=4), and metabolic diseases (n=2).