Selection Of Endocrinology Subspecialty Trainees: Which Applicant Characteristics Are Associated With Performance During Fellowship Training?

Objective: To determine which residency characteristics are associated with performance during endocrinology fellowship training as measured by competency-based faculty evaluation scores and faculty global ratings of trainee performance.Methods: We performed a retrospective review of interview applications from endocrinology fellows who graduated from a single academic institution between 2006 and 2013. Performance measures included competency-based faculty evaluation scores and faculty global ratings. The association between applicant characteristics and measures of performance during fellowship was examined by linear regression.Results: The presence of a laudatory comparative statement in the residency program director's letter of recommendation (LoR) or experience as a chief resident was significantly associated with competency-based faculty evaluation scores (β = 0.22, P = .001; and β = 0.24, P = .009, respectively) and faculty global ratings (β = 0.85, P = .006; and β = 0.96, P = .015, respectively).Conclusion: The presence of a laudatory comparative statement in the residency program director's LoR or experience as a chief resident were significantly associated with overall performance during subspecialty fellowship training. Future studies are needed in other cohorts to determine the broader implications of these findings in the application and selection process.Abbreviations:ABIM = American Board of Internal MedicineACGME = Accreditation Council of Graduate Medical EducationLoR = letter of recommendationUSMLE = United States Medical Licensing Examination     

How probable are antibody cross-reactions?

Antibodies to polypeptides are increasingly being used in research. Their specificity and tight but reversible binding make them ideal for applications such as identification of proteins, immunological quantification or purification, and peptide mapping. Antibodies are also used in medicine to deliver loads to specific sites in tissues, and in electron microscopy as heavy metal conjugates to locate antigens in thin sections. While these techniques depend on specificity of antibody binding, it is occasionally observed that cross-reactions occur. These cross-reactions are attributed to the existence of one or more antibody binding sites common to both polypeptides. It is important to know whether these cross-reactions are expected due to chance alone, or if they are improbable and likely due to some causative agent. Examples of such causative agents might include gene duplication events or convergence due to functional constraints. At the present time, good methods for predicting the probability and therefore the frequency of cross-reactions are unavailable. In this paper we apply some recently reported mathematical results to address the following questions: (1) What is the probability that polyclonal or monoclonal antibodies raised against a given polypeptide will cross-react with another polypeptide due to chance alone? (2) What is the probability that polyclonal or monoclonal antibodies raised against a given polypeptide will cross-react with one or more polypeptides in a pool of polypeptides? Approximate answers to these questions are presented for cases where amino acid compositions of linear polypeptides are known or unknown, but the amino acid sequence of one or more of the polypeptides is not known. Implications of the results for antibody use in protein research are discussed.     

An Adaptive Immune Response in Drosophila?

The ability to mount an adaptive immune response is thought to be an attribute restricted to vertebrates. A new study conducted in Drosophila demonstrates that invertebrate immunity can adapt to an immune challenge and mount a specific immune response.     

Preparation Of 2′-Hydrazino Oligonucleotides And Their Reaction With Aldehydes And 1,3-Diketones

Oligodeoxyribonucleotides that contain a hydrazino nucleoside, 2′-O-(2-hydrazinoethyl)uridine were prepared and shown to react with aldehydes or 1,3-diketones with the formation of hydrazones or pyrazoles, respectively. The method may be applicable for the preparation of oligonucleotide-peptide conjugates.     

Of What Use Is Sex to Bacteria?

Though bacteria are predominantly asexual, the genetic information in their genomes can be expanded and modified through mechanisms that introduce DNA from outside sources. Bacterial sex differs from that of eukaryotes in that it is unidirectional and does not involve gamete fusion or reproduction. The input of DNA during bacterial sex generates diversity in two ways--through the alteration of existing genes by recombination and through the introduction of novel sequences--and each of these processes has been shown to aid in the survival and diversification of lineages.     

IgG cooperativity – Is there allostery? Implications for antibody functions and therapeutic antibody development

A central dogma in immunology is that an antibody's in vivo functionality is mediated by 2 independent events: antigen binding by the variable (V) region, followed by effector activation by the constant (C) region. However, this view has recently been challenged by reports suggesting allostery exists between the 2 regions, triggered by conformational changes or configurational differences. The possibility of allosteric signals propagating through the IgG domains complicates our understanding of the antibody structure-function relationship, and challenges the current subclass selection process in therapeutic antibody design. Here we review the types of cooperativity in IgG molecules by examining evidence for and against allosteric cooperativity in both Fab and Fc domains and the characteristics of associative cooperativity in effector system activation. We investigate the origin and the mechanism of allostery with an emphasis on the C-region-mediated effects on both V and C region interactions, and discuss its implications in biological functions. While available research does not support the existence of antigen-induced conformational allosteric cooperativity in IgGs, there is substantial evidence for configurational allostery due to glycosylation and sequence variations.     

Adrenal Cortical Carcinoma With Late Pulmonary Metastases Causing Clinicical Cushing’s Syndrome: Case Report With Immunohistochemical Analysis Of Steriodogenic Enzyme Production

ObjectiveTo present a case of pulmonary metastases from adrenocortical carcinomas (ACC) that were secreting fully-functional cortisol resulting in clinical Cushing’s syndrome and to compare the steroidogenic enzyme expression in the primary tumor and lung.MethodsWe analyzed and summarized the patient’s medical history, physical examination results, labora tory data, imaging studies, and histopathologic results. The original tumor and the pulmonary metastases were then immunohistochemically evaluated for steroidogenic enzymes.ResultsInitial endocrinological workup revealed hyperandrogenism and adrenocorticotropic hormone (ACTH) independent Cushing’s due to a 4 cm left adrenal mass. The patient was initially diagnosed with an adrenal adenoma. Four years later, the patient developed recurrent Cushing’s syndrome. Repeat magnetic resonance imaging (MRI) showed no adrenal masses; however, chest computed tomography (CT) showed multiple bilateral lung nodules and biopsy revealed metastases of adrenal origin. Upon immunohistochemical analysis, side chain cleavage, 17α hydroxylase, 3β hydroxysteroid dehydrogenase, and 21 hydroxylase immunoreactivity were detected in both the original and pulmonary metastatic lesions with patterns of disorganized steroidogenesis. Dehydroepiandrosterone sulfotransferase (DHEA-ST) immunoreactivity was detected in the original tumor but not in the lung metastases.ConclusionThis case demonstrates some inter esting features of ACC that pose challenges to its management, including the difficulties in establishing the pathologic diagnosis, the potential for fullyfunctional steroidogenesis even in late metastases, and the plasticity of steroidogenic potential in tumor cells. (Endocr Pract. 2012;18:e138-e143)     

Immune response in COVID-19: what is next?

The coronavirus disease 2019 (COVID-19) has been a global pandemic for more than 2 years and it still impacts our daily lifestyle and quality in unprecedented ways. A better understanding of immunity and its regulation in response to SARS-CoV-2 infection is urgently needed. Based on the current literature, we review here the various virus mutations and the evolving disease manifestations along with the alterations of immune responses with specific focuses on the innate immune response, neutrophil extracellular traps, humoral immunity, and cellular immunity. Different types of vaccines were compared and analyzed based on their unique properties to elicit specific immunity. Various therapeutic strategies such as antibody, anti-viral medications and inflammation control were discussed. We predict that with the available and continuously emerging new technologies, more powerful vaccines and administration schedules, more effective medications and better public health measures, the COVID-19 pandemic will be under control in the near future. Subject terms: Infectious diseases, Antimicrobial responses     

Of Mice and Men: Not ExAKTly the Same?

The serine-threonine protein kinase Akt2, also known as PKBβ, has been shown to regulate glucose and lipid metabolism in animal models. In a recent study published in Science, Hussain et al. (2011) report that in human subjects an activating mutation of Akt2 leads to hypoglycemia and, unexpectedly, asymmetric overgrowth.     

Seed development: With or without sex?

In Arabidopsis, mutations in the genes FIE, FIS2 or MEDEA disrupt the normal dependence of seed development on fertilization. The products of these genes are similar to Polycomb group proteins, suggesting possible mechanisms for determining whether seeds can be produced sexually or asexually.