New directions for the treatment of adrenal insufficiency

The following funding bodies supported this work: Biotechnology and Biological Sciences Research Council (BBSRC BB/L00267/1, to LG), Rosetrees Trust (to LG), Barts and The London Charity (417/2235, to LG), EU COFUND (PCOFUND-GA-2013-608765, to LG and GRB). IH is supported by a Medical Research Council (MRC, G0802796) PhD studentship

A Synergistic Antiobesity Effect by a Combination of Capsinoids and Cold Temperature Through Promoting Beige Adipocyte Biogenesis.

Beige adipocytes emerge postnatally within the white adipose tissue in response to certain environmental cues, such as chronic cold exposure. Because of its highly recruitable nature and relevance to adult humans, beige adipocytes have gained much attention as an attractive cellular target for antiobesity therapy. However, molecular circuits that preferentially promote beige adipocyte biogenesis remain poorly understood. We report that a combination of mild cold exposure at 17°C and capsinoids, a nonpungent analog of capsaicin, synergistically and preferentially promotes beige adipocyte biogenesis and ameliorates diet-induced obesity. Gain- and loss-of-function studies show that the combination of capsinoids and cold exposure synergistically promotes beige adipocyte development through the β2-adrenoceptor signaling pathway. This synergistic effect on beige adipocyte biogenesis occurs through an increased half-life of PRDM16, a dominant transcriptional regulator of brown/beige adipocyte development. We document a previously unappreciated molecular circuit that controls beige adipocyte biogenesis and suggest a plausible approach to increase whole-body energy expenditure by combining dietary components and environmental cues

Ion Write Microthermotics: Programing Thermal Metamaterials at the Microscale.

Considerable advances in manipulating heat flow in solids have been made through the innovation of artificial thermal structures such as thermal diodes, camouflages, and cloaks. Such thermal devices can be readily constructed only at the macroscale by mechanically assembling different materials with distinct values of thermal conductivity. Here, we extend these concepts to the microscale by demonstrating a monolithic material structure on which nearly arbitrary microscale thermal metamaterial patterns can be written and programmed. It is based on a single, suspended silicon membrane whose thermal conductivity is locally, continuously, and reversibly engineered over a wide range (between 2 and 65 W/m·K) and with fine spatial resolution (10-100 nm) by focused ion irradiation. Our thermal cloak demonstration shows how ion-write microthermotics can be used as a lithography-free platform to create thermal metamaterials that control heat flow at the microscale

Evolution of Our Understanding of Myeloid Regulatory Cells: From MDSCs to Mregs

The term myeloid-derived suppressor cells (MDSCs) was first suggested in 2007 in order to reflect the origin and function of myeloid cells during immunosuppression in cancer and other pathologic conditions. Emerging evidence suggests that MDSCs suppress CTL and Th1 responses in malignant diseases while they regulate effective immune responses in parasitic and helminth infections as well as Th17 inflammatory response during autoimmune diseases. Based on these data, the term myeloid regulatory cells (Mregs) more accurately reflects their function and interactions with different cells of the immune system during diseased conditions. Here, we provide evidence on the multifaceted function of Mregs during diseased state

A case of polypoid endometriosis mimicking advanced ovarian carcinoma with rapid growth, invasion, and dissemination

Polypoid endometriosis is a rare form of endometriosis characterized by polypoid masses that histologically often resemble endometrial polyps. We report a case of rapidly progressing polypoid endometriosis that was preoperatively assumed to be advanced ovarian cancer. A 46-year-old woman, para 0, underwent laparoscopic myomectomy and left adnexectomy for uterine fibroids and a left ovarian endometrial cyst after administration of gonadotropin releasing hormone (GnRH) agonist for 4 months. Eleven months postoperatively, rapid right ovarian enlargement occurred. CT and MRI (both contrast-enhanced) showed masses in the right adnexa, cecum, sigmoid colon, and omentum, and PET-CT demonstrated increased uptake, suggesting ovarian cancer and peritoneal dissemination. The patient later developed intestinal obstruction, and colonoscopy revealed multiple polypoid lesions in the sigmoid colon. The omental tumor and right adnexa were biopsied during exploratory laparotomy, and diagnosed as polypoid endometriosis with no malignancy by permanent pathology. The right adnexal tumor shrunk markedly after 4 months of GnRH antagonist treatment. Second laparotomy was then performed for right adnexal tumor resection and ileocecectomy. Pathological examination revealed polypoid endometriosis extending from the ovary to the cecal mucosa. The patient has been asymptomatic for over 1 year postoperatively. The sigmoid colon tumor shrunk but is still present.Polypoid endometriosis predominantly affects the ovaries, colon, peritoneum, and omentum of patients in their 40s and 50s. It is a benign disease but is often difficult to distinguish from malignancy preoperatively because it rapidly forms numerous solid lesions. Although polypoid endometriosis is rare, with no specific imaging findings, including it in a differential diagnosis may facilitate preoperative identification

Abscisic acid promotes susceptibility to the rice leaf blight pathogen Xanthomonas oryzae pv oryzae by suppressing salicylic acid-mediated defenses

The plant hormone abscisic acid (ABA) is involved in a wide variety of plant processes, including the initiation of stress-adaptive responses to various environmental cues. Recently, ABA also emerged as a central factor in the regulation and integration of plant immune responses, although little is known about the underlying mechanisms. Aiming to advance our understanding of ABA-modulated disease resistance, we have analyzed the impact, dynamics and interrelationship of ABA and the classic defense hormone salicylic acid (SA) during progression of rice infection by the leaf blight pathogen Xanthomonas oryzae pv. oryzae (Xoo). Consistent with ABA negatively regulating resistance to Xoo, we found that exogenously administered ABA renders rice hypersusceptible to infection, whereas chemical and genetic disruption of ABA biosynthesis and signaling, respectively, led to enhanced Xoo resistance. In addition, we found successful Xoo infection to be associated with extensive reprogramming of ABA biosynthesis and response genes, suggesting that ABA functions as a virulence factor for Xoo. Interestingly, several lines of evidence indicate that this immune-suppressive effect of ABA is due at least in part to suppression of SA-mediated defenses that normally serve to limit pathogen growth. Resistance induced by the ABA biosynthesis inhibitor fluridone, however, appears to operate in a SA-independent manner and is likely due to induction of non-specific physiological stress. Collectively, our findings favor a scenario whereby virulent Xoo hijacks the rice ABA machinery to cause disease and highlight the importance of ABA and its crosstalk with SA in shaping the outcome of rice-Xoo interactions

Sequencing the genome of the Atlantic salmon (Salmo salar)

The International Collaboration to Sequence the Atlantic Salmon Genome (ICSASG) will produce a genome sequence that identifies and physically maps all genes in the Atlantic salmon genome and acts as a reference sequence for other salmonids

Spectral and temporal implementation of Japanese speakers' English vowel categories : a corpus-based study

This study investigates the predictions of second language (L2) speech acquisition models — SLM(-r), PAM(-L2), and L2LP — on how native (L1) Japanese speakers implement the spectral and temporal aspects of L2 American English vowel categories. Data were obtained from 102 L1 Japanese speakers in the J-AESOP corpus, which also includes nativelikeness judgments by trained phoneticians. Spectrally, speakers judged to be non-nativelike showed a strong influence from L1 categories, except L2 /ʌ/ which could be deflected away from L1 /a/ according to SLM(-r) and L2 /ɑː/ which seemed orthographically assimilated to L1 /o/ according to PAM(-L2). More nativelike speakers showed vowel spectra similar to those of native English speakers across all vowels, in accordance with L2LP. Temporally, although speakers tended to equate the phonetic length of English vowels with Japanese phonemic length distinctions, segment-level L1-L2 category similarity was not a significant predictor of the speakers’ nativelikeness. Instead, the implementation of prosodic-level factors such as stress and phrase-final lengthening were better predictors. The results highlight the importance of suprasegmental factors in successful category learning and also reveal a weakness in current models of L2 speech acquisition, which focus primarily on the segmental level. Theoretical and pedagogical implications are discussed