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Enterotoxigenic (ETBF) strains of Bacteroides fragilis are the subset of strains that secrete a toxin called fragilysin (Bft). Although ETBF strains are known to cause diarrheal disease and have recently been associated with colorectal cancer, they have not been well characterized. By sequencing the complete genome of four ETBF strains, we found that these strains exhibit considerable variation at the genomic level. Only a small number of genes that are located primarily in the Bft pathogenicity island (BFT PAI) and the flanking CTn86 conjugative transposon are conserved in all four strains and a fifth strain whose genome was previously sequenced. Interestingly, phylogenetic analysis strongly suggests that the BFT PAI was acquired by non-toxigenic (NTBF) strains multiple times during the course of evolution. At the phenotypic level, we found that the ETBF strains were less fit than the NTBF strain NCTC 9343 and were susceptible to a growth-inhibitory protein that it produces. The ETBF strains also showed a greater tendency to form biofilms, which may promote tumor formation, than NTBF strains. Although the genomic diversity of ETBF strains raises the possibility that they vary in their pathogenicity, our experimental results also suggest that they share common properties that are conferred by different combinations of non-universal genetic elements.

Senescence is a cellular defense mechanism that helps cells prevent acquired damage, but chronic senescence, as in aging, can contribute to the development of age-related tissue dysfunction and disease. Previous studies clearly show that removal of senescent cells can help prevent tissue dysfunction and extend healthspan during aging. Senescence increases with age in the skeletal system, and selective depletion of senescent cells or inhibition of their senescence-associated secretory phenotype (SASP) has been reported to maintain or improve bone mass in aged mice. This suggests that promoting the selective removal of senescent cells, via the use of senolytic agents, can be beneficial in the treatment of aging-related bone loss and osteoporosis. Navitoclax (also known as ABT-263) is a chemotherapeutic drug reported to effectively clear senescent hematopoietic stem cells, muscle stem cells, and mesenchymal stromal cells in previous studies, but its effects on bone mass had not yet been reported. Therefore, the purpose of this study was to assess the effects of short-term navitoclax treatment on bone mass and osteoprogenitor function in old mice. Aged (24 month old) male and female mice were treated with navitoclax (50 mg/kg body mass daily) for 2 weeks. Surprisingly, despite decreasing senescent cell burden, navitoclax treatment decreased trabecular bone volume fraction in aged female and male mice (-60.1% females, -45.6% males), and BMSC-derived osteoblasts from the navitoclax treated mice were impaired in their ability to produce a mineralized matrix (-88% females, -83% males). Moreover, administration of navitoclax decreased BMSC colony formation and calcified matrix production by aged BMSC-derived osteoblasts, similar to effects seen with the primary BMSC from the animals treated . Navitoclax also significantly increased metrics of cytotoxicity in both male and female osteogenic cultures (+1.0 to +11.3 fold). Taken together, these results suggest a potentially harmful effect of navitoclax on skeletal-lineage cells that should be explored further to definitively assess navitoclax's potential (or risk) as a therapeutic agent for combatting age-related musculoskeletal dysfunction and bone loss.

إن المعلومات الجديدة التي تتراكم يوميا تنسف الحدود المدركة بين البشر والحيوانات، وتجبرنا على إعادة النظر في الأفكار النمطية العتيقة وضيق الأفق حول قدرات الحيوانات الفكرية والأدائية والشعورية، في هذا الكتاب \"العدالة في عالم الحيوان\" نقدم الحجة على أن الحيوانات تمارس مجموعة كبيرة من السلوكيات الأخلاقية، وأن حياتها الجماعية تتأثر بأنماطها السلوكية، ويؤدي ما هو مفترض وما هو واجب فيما يتعلق بالصواب والخطأ دورا مهما في تفاعلاتها الاجتماعية، كما هو الحال بالضبط في تفاعلاتنا وإذا كنت تشعر ببعض الريبة فإننا ندعوك لأن تطلق العنان لعقلك تنظر إلى الحيوانات من منظور مختلف، ونأمل أن يشرع القراء في تغيير وجهات نظرهم حول فكرة السلوك الأخلاقي في عالم الحيوان.

To understand differences in host- Candida albicans interactions that occur during colonization of healthy or compromised hosts, production of phenotypic variants and colonization of healthy or immunodeficient mice by C. albicans were studied. We showed that activity of the transcription factor Efg1p exhibited cell-to-cell variability and identified Efg1p as a major regulator of colonization. In C. albicans populations colonizing the murine gastrointestinal tract, average expression of EFG1 differed depending on the immune status of the host. We propose that cellular heterogeneity in Efg1p activity allows the C. albicans colonizing population to differ depending on the immune status of the host, because selective pressure from a healthy host alters the composition of the population. These data are the first demonstration that differences in host immune status are associated with differences in gene expression in colonizing C. albicans cells. Altered gene expression in organisms colonizing immunocompromised hosts may begin the transition of C. albicans from a commensal to a pathogen. IMPORTANCE In healthy people, the fungus Candida albicans colonizes the gastrointestinal tract and other sites without producing obvious pathology. In an immunocompromised patient, the organism can cause serious disease. The demonstration that the expression and activity of the C. albicans transcription factor Efg1p differs during colonization of healthy or immunocompromised mice shows that the organism adjusts its physiology when colonizing different hosts. Further, the effects of a healthy host on a heterogeneous C. albicans population containing cells with different levels of Efg1p activity show that selective pressure in the host can change the makeup of the population, allowing the population to respond to host immune status. The ability to sense host status may be key to the ability of C. albicans to colonize as a harmless commensal in some hosts but become a deadly pathogen in others. In healthy people, the fungus Candida albicans colonizes the gastrointestinal tract and other sites without producing obvious pathology. In an immunocompromised patient, the organism can cause serious disease. The demonstration that the expression and activity of the C. albicans transcription factor Efg1p differs during colonization of healthy or immunocompromised mice shows that the organism adjusts its physiology when colonizing different hosts. Further, the effects of a healthy host on a heterogeneous C. albicans population containing cells with different levels of Efg1p activity show that selective pressure in the host can change the makeup of the population, allowing the population to respond to host immune status. The ability to sense host status may be key to the ability of C. albicans to colonize as a harmless commensal in some hosts but become a deadly pathogen in others.

\"A working mother strives to balance her demanding career with the stress of raising two young children and maintaining a healthy marriage in this comedy adapted from the best-selling novel by Allison Pearson. By day, Kate Reddy (Sarah Jessica Parker) works for a Boston-based financial management firm; by night, she's a devoted mother to two adoring children and the happily married wife of out-of-work architect Richard (Greg Kinnear). Though balancing those two worlds has its fair share of challenges, Kate generally manages to come out on top thanks to the support of her best friend, Allison (Christina Hendricks), who's had plenty of experience balancing kids and a career. Meanwhile, on the other end of the spectrum, Kate's sharp-as-a-tack junior associate assistant, Momo (Olivia Munn), possesses a fear of children and a strong work ethic. Just when Kate lands a lucrative new account that will see her traveling across the country on a regular basis, however, her new business associate Jack (Pierce Brosnan) reveals his flirtatious side and Richard receives a job offer he can't turn down. Though it looks as if Kate and Richard couldn't possibly take on any more responsibility, the demands of modern living ensure they'll never have a dull moment, even if they try\"--Allmovie.com, September 28, 2018.

Background Doxycycline is currently the only tetracycline-class antibiotic recommended for malaria prophylaxis. Omadacycline, a semisynthetic aminomethylcycline approved for treatment of adults with community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections, has a well-established safety profile. This study evaluated the in vitro activity of omadacycline against Plasmodium falciparum and Plasmodium cynomolgi and its in vivo efficacy against Plasmodium berghei in experimental malaria models to assess its potential as an antimalarial drug. Methods Fluorescence-based assays were used to assess the in vitro blood and liver stage activity of omadacycline and doxycycline against P. falciparum and P. cynomolgi laboratory clones. In vivo liver and early-stage blood stage efficacy were evaluated in a murine model of P. berghei infection, utilizing in vivo imaging of luciferase-expressing P. berghei (ANKA strain) sporozoites in female albino C57Bl/6 mice. Parasitaemia was monitored by flow cytometry for up to 30 days post-infection. Results Omadacycline demonstrated comparable in vitro activity to doxycycline against both drug-sensitive and drug-resistant P. falciparum clones, while doxycycline showed reduced activity against two drug-resistant clones. Notably, omadacycline exhibited superior anti-schizont activity in the P. cynomolgi liver stage assay. In the P. berghei murine model, omadacycline was efficacious in both liver and early blood stages compared to the untreated control group, and demonstrated improved survival compared to doxycycline. Conclusions Omadacycline demonstrated enhanced antimalarial efficacy over doxycycline in vitro in liver stage activity and in overcoming resistance in the blood stage, and in survival in an in vivo model of P. berghei infection. These findings support further investigation of omadacycline as a potential candidate for malaria prophylaxis and treatment.

Purpose of ReviewFibrodysplasia ossificans progressiva (FOP) is a debilitating rare disease known for episodic endochondral heterotopic ossification (HO) caused by gain-of-function mutations in ACVR1/ALK2. However, disease severity varies among patients with identical mutations suggesting disease-modifying factors, including diet, may have therapeutic implications. The roles of vitamin D3 in calcium metabolism and chondrogenesis are known, but its effects on BMP signaling and chondrogenesis are less studied. This review attempts to assess the possibility of vitamin D’s effects in FOP by exploring relevant intersections of VD3 with mechanisms of FOP flares.Recent FindingsIn vitro and in vivo studies suggest vitamin D suppresses inflammation, while clinical studies suggest that vitamin D3 protects against arteriosclerosis and inversely correlates with non-genetic intramuscular HO. However, the enhancement of chondrogenesis, BMP signaling, and possibly Activin A expression by vitamin D may be more relevant in FOP.SummaryThere appears to be little potential for vitamin D to reduce HO in FOP, but testing the potential for excess vitamin D to promote HO may be warranted.

Objective Transition from pediatric to adult healthcare systems is a difficult process for young adults with Type 1 Diabetes (T1D) and most patients experience a deterioration in disease control. Mental health (MH) disorders are common in individuals with T1D and are believed to play a role in disease control and transition of care. We evaluated the association between the presence of pediatric MH disorder and measures of success in diabetes care in young adults who recently transitioned to adult care. Research Design and Methods Retrospective cohort study of young adults in a large adult endocrinology system who transitioned from a pediatric hospital system after 2009. MH disorders were diagnosed by clinical pediatric psychologists during routine care at the pediatric hospital. Measurements of Hemoglobin A1c, diabetes‐related emergencies, clinic attendance and intervals in transition were assessed and compared between the pediatric and adult hospital systems. Results 237 young adults were identified and 100 (42%) of these were diagnosed with a MH disorder during pediatric care. Presence of a MH disorder was associated with higher Hemoglobin A1c levels prior to transition and increased rates of diabetes‐related hospitalizations during the transition interval. Patients with a MH disorder were less likely to establish a pattern of consistent follow up after transition (p = 0.021). Conclusions MH disorders are common and predict greater challenges with diabetes management and less effective transition into the adult endocrinology system. Early recognition of MH disorders may allow for allocation of more proactive and intensive support for affected patients.