Thiopurine S-methyltransferase testing for averting drug toxicity: a meta-analysis of diagnostic test accuracy.

Pharmacogenomics J. 2016 May 24;

Authors: Zur RM, Roy LM, Ito S, Beyene J, Carew C, Ungar WJ

Abstract
Thiopurine S-methyltransferase (TPMT) deficiency increases the risk of serious adverse events in persons receiving thiopurines. The objective was to synthesize reported sensitivity and specificity of TPMT phenotyping and genotyping using a latent class hierarchical summary receiver operating characteristic meta-analysis. In 27 studies, pooled sensitivity and specificity of phenotyping for deficient individuals was 75.9% (95% credible interval (CrI), 58.3-87.0%) and 98.9% (96.3-100%), respectively. For genotype tests evaluating TPMT*2 and TPMT*3, sensitivity and specificity was 90.4% (79.1-99.4%) and 100.0% (99.9-100%), respectively. For individuals with deficient or intermediate activity, phenotype sensitivity and specificity was 91.3% (86.4-95.5%) and 92.6% (86.5-96.6%), respectively. For genotype tests evaluating TPMT*2 and TPMT*3, sensitivity and specificity was 88.9% (81.6-97.5%) and 99.2% (98.4-99.9%), respectively. Genotyping has higher sensitivity as long as TPMT*2 and TPMT*3 are tested. Both approaches display high specificity. Latent class meta-analysis is a useful method for synthesizing diagnostic test performance data for clinical practice guidelines.The Pharmacogenomics Journal advance online publication, 24 May 2016; doi:10.1038/tpj.2016.37.

PMID: 27217052 [PubMed - as supplied by publisher]

Clinical-pharmacogenetic predictive models for MTX discontinuation due to adverse events in rheumatoid arthritis.

Pharmacogenomics J. 2016 May 24;

Authors: Jenko B, Lusa L, Tomsic M, Praprotnik S, Dolzan V

Abstract
We describe a novel approach to investigate and evaluate combined effect of a large number of clinical and pharmacogenetic factors on treatment outcome. We have used this approach to investigate predictors of methotrexate (MTX)-induced adverse events (AEs) leading to treatment discontinuation in rheumatoid arthritis (RA) patients. In total, 333 RA patients were genotyped for 34 polymorphisms in MTX transporters, folate and adenosine pathways. The effect of clinical and pharmacogenetic factors was assessed with penalized regression in the cause-specific Cox proportional hazards model. The predictive capacity was evaluated with the area under time-dependent receiver operating characteristic curve where cross-validation was applied. SLC19A1, ABCG2, ADORA3 and TYMS were associated with discontinuation because of AEs in clinical-pharmacogenetic model. Cross-validation showed that both clinical-pharmacogenetic model and nongenetic model had worthless predictive ability for MTX discontinuation because of AEs. These models could be further improved, either with additional polymorphisms or with epigenetic predictors.The Pharmacogenomics Journal advance online publication, 24 May 2016; doi:10.1038/tpj.2016.36.

PMID: 27217051 [PubMed - as supplied by publisher]

Malignant Pyoderma Associated with Granulomatosis with Polyangiitis (Wegener Granulomatosis) as a Unique Indication for Facial Vascularized Composite Allotransplantation: Part I.

Plast Reconstr Surg. 2016 Jun;137(6):1007e-1015e

Authors: Gastman B, Hashem AM, Djohan R, Bernard S, Hendrickson M, Schwarz G, Gharb BB, Rampazzo A, Fernandez A, Zins J, Hoffman GS, Doumit G, Siemionow M, Papay F

Abstract
BACKGROUND: Granulomatosis with polyangiitis (Wegener granulomatosis) is a rare disease that commonly starts in the craniofacial region and can lead to considerable facial disfigurement. Granulomas and vasculitis, however, can involve many other tissues (especially pulmonary and renal). Dermatologic and subcutaneous components can lead to malignant pyoderma.
METHODS: The authors describe a unique pathologic condition, where significant Le Fort type trauma was associated with subsequent development of granulomatosis with polyangiitis and malignant pyoderma. Successive operations to excise necrotic tissue and reconstruct the defects were followed by worsening inflammation and tissue erosions. Trauma and surgery in proximity to the eye and sinuses masked the initial clinical presentation and led to delay in diagnosis and disease progression. The resultant facial disfigurement and tissue loss were substantial.
RESULTS: Despite multiple confounding factors, accurate diagnosis was eventually established. This was based on persistence of sinus inflammations in the absence of infective agents, proven sterility of lung lesions, and antineutrophil cytoplasmic antibody positivity with proteinase 3 specificity. Skin lesion biopsy specimens were identified as pyoderma gangrenosum and later as malignant pyoderma. Institution of immunosuppressive therapy allowed successful control of the disease and wound healing. The resulting craniofacial destruction, however, necessitated facial vascularized composite allotransplantation.
CONCLUSION: Recognition of this rare pathologic association is essential, to prevent delays in diagnosis and treatment that can lead to major craniofacial tissue loss.
CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

PMID: 27219252 [PubMed - as supplied by publisher]

[Peutz-Jeghers syndrome manifested as massive melæna at CHU-JRA Madagascar hospital: a case report].

Pan Afr Med J. 2016;23:78

Authors: Martinetti AF, Andriantsoa RM, Andriambelo RT, Nicole RR, Enintsoa RN

Abstract
Peutz-Jeghers syndrome (SPJ) is characterized by intestinal hamartomatous polyps in association with mucocutaneous lentiginosis. Patients are exposed to mechanical and bleeding complications. It is a cancer predisposition syndrome. Our study highlights the diagnostic criteria for Peutz-Jeghers syndrome (SPJ), the complications and the therapeutic progresses in patient care. We report the case of a 32-year-old male presenting with a massive melaena. It was hospitalized in the surgical intensive care unit with hypovolemic shock difficult to control. This required surgical intervention to stop bleeding. We found a hamartomatous polyps in the small intestine which caused bleeding. Peutz Jeghers Syndrome was diagnosed on the basis of labial lentigines during childhood. Clinical and paraclinical explorations did not reveal the presence of cancer. In Madagascar, this disease is still poorly understood. In the literature, the diagnosis of Peutz Jeghers syndrome is based on clinical findings or on the presence of complications such as haemorrhage, invagination or bowel obstruction. In our case, the disease was complicated by gastrointestinal bleeding with hypovolemic shock. Endoscopic polypectomy using double-balloon enteroscopy can reduce emergency small bowel surgery. Peutz-Jeghers syndrome is a rare disease. Despite this, it is important for clinicians to know it and to take it into consideration in case of gastrointestinal bleeding.

PMID: 27217901 [PubMed - in process]

Ectopic adrenocorticotropic hormone syndrome caused by neuroendocrine tumors of the thymus: 30-year experience with 16 patients at a single institute in the People's Republic of China.

Onco Targets Ther. 2016;9:2193-201

Authors: Chen YY, Li SQ, Liu HS, Qin YZ, Li L, Huang C, Bi YL, Meng YX, He J, Zhou XY, Ma DJ

Abstract
BACKGROUND AND PURPOSE: Thymic neuroendocrine carcinomas (TNECs) are extremely uncommon. Certain cases of TNECs can produce the adrenocorticotropic hormone (ACTH) and cause ectopic ACTH syndrome (EAS). The current literature on this topic consists mainly of case reports, and therapeutic guidelines are lacking. The aim of this study was to discuss the diagnosis, surgical management, and prognosis of EAS caused by TNECs to improve clinical experience with this rare disease.
METHODS: From June 1984 to June 2014, at the Peking Union Medical College Hospital, the surgical interventions and follow-up outcomes of 16 consecutive patients (eight men and eight women) with EAS caused by TNECs were retrospectively analyzed.
RESULTS: The median age was 32.5 years (range: 13-47 years), and the median disease duration was 8.5 months (range: 1-150 months). All patients presented with clinical and biochemical evidence indicating a diagnosis of Cushing's syndrome. Contrast-enhanced thoracic computed tomography scans were critical to locating the ACTH-producing tumor and evaluating the feasibility of resection. All patients underwent surgery. One patient died of septicemia in the intensive care unit 2 weeks after surgery. No other morbidity or mortality occurred during the perioperative period. The median overall survival (OS) was 41 months (95% CI: 30.3-51.7 months), and the progression-free survival was 28 months (95% CI: 21.6-34.3 months). Both overall survival (P=0.002) and progression-free survival (P=0.030) improved significantly after complete resection.
CONCLUSION: TNEC is an extremely aggressive disease that should be considered when treating patients with Cushing's syndrome due to ectopic ACTH secretion. In particular, all suspected patients should undergo contrast-enhanced thoracic computed tomography scans to facilitate early diagnosis. The current first-line treatment is surgical resection, and complete resection is a favorable prognostic factor. However, additional patients and a longer follow-up will be needed to determine the variables that are predictive of survival and to improve patient prognosis.

PMID: 27217765 [PubMed]

Clear Cell Mypepithelial Carcinoma of the Base Tongue Managed by the Mandible Preserving Pull-Through Oropharyngectomy Approach.

Indian J Surg Oncol. 2015 Sep;6(3):263-6

Authors: Krishnamurthy A

Abstract
Myoepithelial carcinoma (MC) is rare disease that comprises of only about 2 % of all salivary gland carcinomas and MC that focally or predominantly displays clear cell-type tumor cells are considered as CCMC. We recently got to treat a rare case of a base tongue clear cell myoepithelial carcinoma. (CCMC) Our patient, to the best of our knowledge is the second case of base tongue CCMC and the first with metastatic involvement of the cervical lymph nodes. We successfully managed the tumor using the "mandible preserving pull-through oropharyngectomy approach" Knowledge of the different surgical approaches and techniques is thus vital for better oncologic, functional and aesthetic outcomes following surgery for tumors especially in challenging sub sites like the oropharynx.

PMID: 27217675 [PubMed]

[A Case of Inflammatory Myofibroblastic Tumor of Urinary Bladder].

Hinyokika Kiyo. 2016 Apr;62(4):201-4

Authors: Tanaka K, Ikeda A, Miyakawa T, Komine M, Tsutsumi M, Ishikawa S, Kawai K, Nishiyama H

Abstract
A 61-year-old man presenting with voiding pain was diagnosed with a bladder tumor by ultrasound in another hospital, and was subsequently referred to our hospital. Cystoscopy showed a nodular tumor and surrounding edematous mucosa in the right wall of the bladder. Initially, we suspected bladder invasion of gastrointestinal malignancy, but abdominal computed tomography, magnetic resonance imaging, and a series of tumor marker tests revealed no abonormalities. We performed transurethral resection of the bladder tumor under the clinical diagnosis of a submucosal tumor originating from the bladder wall. Histopathological examination revealed spindle cell proliferation, which was positively stained with anti-anaplastic lymphoma kinase (ALK) antibody. Based on the findings, the diagnosis of an inflammatory myofibroblastic tumor (IMT) was made. Therefore, we performed partial cystectomy to reduce the risk of local recurrence. The pathological diagnosis was IMT, and the surgical margins were negative. Bladder IMT is a rare disease, and surgical resection is the only recommended treatment. In the literature, if completely resected, the prognosis of patients with bladder IMT is excellent. Also, in the present case, no recurrence has been detected for over 6 months.

PMID: 27217015 [PubMed - in process]

Evidence of pathogenicity of a mutation in 3' untranslated region causing mild haemophilia A.

Haemophilia. 2016 May 24;

Authors: Pezeshkpoor B, Berkemeier AC, Czogalla KJ, Oldenburg J, El-Maarri O

Abstract
INTRODUCTION: Despite the high mutation detection rate, in a small group of haemophilia A patients, using current screening methods, no causal mutation in F8 can be detected. In such cases, the causal mutation might be in the non-coding sequences of F8.
AIM: Rarely, mutations in non-coding sequences reveal a pivotal role. Here, we analysed a mild haemophilia A patient harbouring a mutation in the 3' untranslated region (UTR) of F8 and elucidated the molecular mechanism leading to haemophilia phenotype.
METHODS: To find the causal mutation, the complete F8 genomic region was analysed by next generation sequencing. The effect of the identified alteration on F8 expression was evaluated in silico and analysed for the splicing effect at mRNA level. Moreover, in vitro studies using a luciferase reporter system were performed to functionally analyse the mutation.
RESULTS: We identified an alteration in the 3' UTR (c.*56G>T) as the only change in F8 gene. Pedigree analysis showed a segregation pattern for three affected members for the presumptive mutation. Moreover, the variant was predicted in silico to create a new donor splice site, which was also detected at mRNA level, resulting in a 159 bp deletion in 3' UTR of F8. Finally, the variant showed reduced expression of the gene reporter firefly luciferase in cell line expression analysis.
CONCLUSION: Our results advocate the patient specific c.*56G>T base change in the 3' UTR to be a disease-associated mutation leading to alternative splicing explaining the mild haemophilia A phenotype.

PMID: 27216882 [PubMed - as supplied by publisher]

Combined immunodeficiency in a patient with mosaic monosomy 21.

Immunol Res. 2016 May 24;

Authors: Rechavi E, Levy-Mendelovich S, Stauber T, Shamash J, Reinstein S, Vernitsky H, Adam D, Simon AJ, Lev A, Raas-Rothschild A, Somech R

Abstract
Monosomy 21 is an extremely rare genetic disorder presenting with a wide array of symptoms. Recurrent infections, some life threatening, have been reported in several monosomy 21 patients and attributed to an, as of yet, undefined immunodeficiency. Here we report on a 3-year-old boy with mosaic monosomy 21 who presented with clinical and laboratory evidence of immunodeficiency. Despite suffering from infections highly suggestive of a cell-mediated immune defect, the patient's T cells displayed normal counts, subsets and proliferation capability. T cell receptor repertoire was diverse, and de novo T cell production was intact. Consistent with earlier case reports, our patient displayed mildly low B cell counts with hypogammaglobulinemia. B cell subsets demonstrated mainly naïve and marginal zone B cells that have not undergone class switch. Subsequently, IgG, IgA and IgE levels were near absent, whereas IgM level was normal. De novo B cell production and B cell receptor diversity were normal. Together, these results are indicative of a defect in immunoglobulin class switching as the principal cause of immunodeficiency in monosomy 21. A better understanding of the immunodeficiency in this syndrome will enable targeted treatment and prevention of infections in order to prevent morbidity and mortality in these patients.

PMID: 27216863 [PubMed - as supplied by publisher]

Towards rational drug treatment of Lesch-Nyhan disease.

Mol Genet Metab. 2016 May 9;

Authors: Seifert R

Abstract
Lesch-Nyhan disease (LND) is a rare X-chromosomal purine metabolism disorder. LND is characterized by self-injurious behavior (SIB) for which there is no drug treatment. This commentary places a recent clinical study by Khasnavis et al. (Mol. Genetic. Metab., in press) on drug treatment of SIB into a broader context. Although the study by Khasnavis et al. was no break-through in terms of "positive" results, nonetheless, it presents an excellent model of how clinical studies in general and clinical studies on rare diseases should be conducted.

PMID: 27216368 [PubMed - as supplied by publisher]

Takayasu arteritis presenting with malignant hypertension; a rare manifestation of a rare disease: a case report and review of the literature.

Trop Doct. 2016 May 22;

Authors: Patel B, Tiwari A, Dubey SR, Bhatt GC, Tiwari P, Bhan BD

Abstract
Takayasu arteritis (TA) is a chronic inflammatory and obliterative disease of large vessels, which mainly affects the aorta and its major branches. TA can lead to renal failure and renovascular hypertension in 60% of patients; it is rare in children aged <10 years and, more rarely, it presents with malignant hypertension in the paediatric age group. Here we present a case of 9-year-old boy with TA who presented with malignant hypertension and required surgical intervention to control the blood pressure. Subsequently, his medications were titrated using 24 h ambulatory blood pressure monitoring (ABPM) and is doing well on follow-up.

PMID: 27216226 [PubMed - as supplied by publisher]

Contemporary management of fibrolamellar hepatocellular carcinoma: diagnosis, treatment, outcome, prognostic factors, and recent developments.

World J Surg Oncol. 2016;14(1):151

Authors: Kassahun WT

Abstract
Fibrolamellar hepatocellular carcinoma (FL-HCC) is a malignant liver tumor which is thought to be a variant of conventional hepatocellular carcinoma (HCC). It accounts for a small proportion of HCC cases and occurs in a distinctly different group of patients which are young and usually not in the setting of chronic liver disease. The diagnosis of FL-HCC requires the integration of clinical information, imaging studies, and histology. In terms of the treatment options, the only potentially curative treatment option for patients who have resectable disease is surgery either liver resection (LR) or liver transplantation (LT). When performed in a context of aggressive therapy, long-term outcomes after surgery, particularly liver resection for FL-HCC, were favorable. The clinical outcome of patients with unresectable disease is suboptimal with median survival of less than 12 months. The aim of this review is to update the available evidence on diagnosis, treatment options, outcome predictors, and recent developments of patients with this rare disease and to provide a summarized overview of the available literature.

PMID: 27215576 [PubMed - in process]

Free-thiamine is a potential biomarker of thiamine transporter-2 deficiency: a treatable cause of Leigh syndrome.

Brain. 2016 Jan;139(Pt 1):31-8

Authors: Ortigoza-Escobar JD, Molero-Luis M, Arias A, Oyarzabal A, Darín N, Serrano M, Garcia-Cazorla A, Tondo M, Hernández M, Garcia-Villoria J, Casado M, Gort L, Mayr JA, Rodríguez-Pombo P, Ribes A, Artuch R, Pérez-Dueñas B

Abstract
Thiamine transporter-2 deficiency is caused by mutations in the SLC19A3 gene. As opposed to other causes of Leigh syndrome, early administration of thiamine and biotin has a dramatic and immediate clinical effect. New biochemical markers are needed to aid in early diagnosis and timely therapeutic intervention. Thiamine derivatives were analysed by high performance liquid chromatography in 106 whole blood and 38 cerebrospinal fluid samples from paediatric controls, 16 cerebrospinal fluid samples from patients with Leigh syndrome, six of whom harboured mutations in the SLC19A3 gene, and 49 patients with other neurological disorders. Free-thiamine was remarkably reduced in the cerebrospinal fluid of five SLC19A3 patients before treatment. In contrast, free-thiamine was slightly decreased in 15.2% of patients with other neurological conditions, and above the reference range in one SLC19A3 patient on thiamine supplementation. We also observed a severe deficiency of free-thiamine and low levels of thiamine diphosphate in fibroblasts from SLC19A3 patients. Surprisingly, pyruvate dehydrogenase activity and mitochondrial substrate oxidation rates were within the control range. Thiamine derivatives normalized after the addition of thiamine to the culture medium. In conclusion, we found a profound deficiency of free-thiamine in the CSF and fibroblasts of patients with thiamine transporter-2 deficiency. Thiamine supplementation led to clinical improvement in patients early treated and restored thiamine values in fibroblasts and cerebrospinal fluid.

PMID: 26657515 [PubMed - indexed for MEDLINE]

Mutations in the MORC2 gene cause axonal Charcot-Marie-Tooth disease.

Brain. 2016 Jan;139(Pt 1):62-72

Authors: Sevilla T, Lupo V, Martínez-Rubio D, Sancho P, Sivera R, Chumillas MJ, García-Romero M, Pascual-Pascual SI, Muelas N, Dopazo J, Vílchez JJ, Palau F, Espinós C

Abstract
Charcot-Marie-Tooth disease (CMT) is a complex disorder with wide genetic heterogeneity. Here we present a new axonal Charcot-Marie-Tooth disease form, associated with the gene microrchidia family CW-type zinc finger 2 (MORC2). Whole-exome sequencing in a family with autosomal dominant segregation identified the novel MORC2 p.R190W change in four patients. Further mutational screening in our axonal Charcot-Marie-Tooth disease clinical series detected two additional sporadic cases, one patient who also carried the same MORC2 p.R190W mutation and another patient that harboured a MORC2 p.S25L mutation. Genetic and in silico studies strongly supported the pathogenicity of these sequence variants. The phenotype was variable and included patients with congenital or infantile onset, as well as others whose symptoms started in the second decade. The patients with early onset developed a spinal muscular atrophy-like picture, whereas in the later onset cases, the initial symptoms were cramps, distal weakness and sensory impairment. Weakness and atrophy progressed in a random and asymmetric fashion and involved limb girdle muscles, leading to a severe incapacity in adulthood. Sensory loss was always prominent and proportional to disease severity. Electrophysiological studies were consistent with an asymmetric axonal motor and sensory neuropathy, while fasciculations and myokymia were recorded rather frequently by needle electromyography. Sural nerve biopsy revealed pronounced multifocal depletion of myelinated fibres with some regenerative clusters and occasional small onion bulbs. Morc2 is expressed in both axons and Schwann cells of mouse peripheral nerve. Different roles in biological processes have been described for MORC2. As the silencing of Charcot-Marie-Tooth disease genes have been associated with DNA damage response, it is tempting to speculate that a deregulation of this pathway may be linked to the axonal degeneration observed in MORC2 neuropathy, thus adding a new pathogenic mechanism to the long list of causes of Charcot-Marie-Tooth disease.

PMID: 26497905 [PubMed - indexed for MEDLINE]

Distinct cardiac phenotype between two homozygotes born in a village with accumulation of a genetic deficiency of adipose triglyceride lipase.

Int J Cardiol. 2015 Aug 1;192:30-2

Authors: Higashi M, Hirano K, Kobayashi K, Ikeda Y, Issiki A, Otsuka T, Suzuki A, Yamaguchi S, Zaima N, Hamada S, Hanada H, Suzuki C, Nakamura H, Nagasaka H, Miyata T, Miyamoto Y, Kobayashi K, Naito H, Toda T

PMID: 25985012 [PubMed - indexed for MEDLINE]

Recent developments in multiplexing techniques for immunohistochemistry.

Expert Rev Mol Diagn. 2015;15(9):1171-86

Authors: Dixon AR, Bathany C, Tsuei M, White J, Barald KF, Takayama S

Abstract
Methods to detect immunolabeled molecules at increasingly higher resolutions, even when present at low levels, are revolutionizing immunohistochemistry (IHC). These technologies can be valuable for the management and examination of rare patient tissue specimens, and for improved accuracy of early disease detection. The purpose of this article is to highlight recent multiplexing methods that are candidates for more prevalent use in clinical research and potential translation to the clinic. Multiplex IHC methods, which permit identification of at least 3 and up to 30 discrete antigens, have been divided into whole-section staining and spatially-patterned staining categories. Associated signal enhancement technologies that can enhance performance and throughput of multiplex IHC assays are also discussed. Each multiplex IHC technique, detailed herein, is associated with several advantages as well as tradeoffs that must be taken into consideration for proper evaluation and use of the methods.

PMID: 26289603 [PubMed - indexed for MEDLINE]

[Identification of proteomic biomarkers of preeclampsia using protein microarray and tandem mass spectrometry].

Postepy Hig Med Dosw (Online). 2015;69:562-70

Authors: Charkiewicz K, Jasinska E, Laudanski P

Abstract
Preeclampsia (PE) is the leading cause of death of the fetus and the mother. The exact pathomechanism has not so far been clarified. PE coexists with many other diseases, but it is often difficult to explain the association between them and find a clear reason for their occurrence. There are many predictive factors, but none are highly specific in preeclampsia. The diagnosis of preeclampsia seems to be very complex, which is another argument for the exploration of knowledge on this subject. Although many of the discoveries have hitherto been made in the field of proteomics, still no single specific biomarker of preeclampsia has been discovered. Research at the genome level is important because it can help us understand the genetic predisposition of patients affected by this disease. Nevertheless, researchers have recently become more interested in the pathophysiology of PE, and they are trying to answer the question: what is the real, direct cause of preeclampsia? Thus, the discovery of a protein that is a good predictor of preeclampsia development would significantly accelerate the medical care of pregnant women, and consequently reduce the risk of occurrence of HELLP syndrome and fetal death. Apart from the predictive and diagnostic function, such a discovery would help us to better understand the pathogenesis of preeclampsia and to find in the future a medical drug to suppress this disease. In order to make a breakthrough in this field, scientists need to use the most modern methods of proteomics, which allow for the analysis of small amounts of biological material in the shortest possible time, thereby giving a lot of information about existing proteins in the sample. Such optimization allows two methods, most commonly used by researchers: tandem mass spectrometry and protein microarray technique.

PMID: 25983295 [PubMed - indexed for MEDLINE]

The bovine milk microbiota: insights and perspectives from -omics studies.

Mol Biosyst. 2016 May 24;

Authors: Addis MF, Tanca A, Uzzau S, Oikonomou G, Bicalho RC, Moroni P

Abstract
Recent significant progress in culture-independent techniques, together with the parallel development of -omics technologies and data analysis capabilities, have led to a new perception of the milk microbiota as a complex microbial community with great diversity and multifaceted biological roles, living in an environment that was until recently believed to be sterile. In this review, we summarize and discuss the latest findings on the milk microbiota in dairy cows, with a focus on the role it plays in bovine physiology and health. Following an introduction on microbial communities and the importance of their study, we present an overview of the -omics methods currently available for their characterization, and outline the potential offered by a systems biology approach encompassing metatranscriptomics, metaproteomics, and metametabolomics. Then, we review the recent discoveries on the dairy cow milk microbiome enabled by the application of -omics approaches. Learning from studies in humans and in the mouse model, and after a description of the endogenous route hypothesis, we discuss the role of the milk microbiota in the physiology and health of both the mother and the offspring, and report how it can be changed by farming practices and during infection. In conclusion, we shortly outline the impact of the milk microbiota on the quality of milk and of dairy products.

PMID: 27216801 [PubMed - as supplied by publisher]

Drug Design based on Protein Structure Network.

Mini Rev Med Chem. 2016 May 24;

Authors: Liang Z, Hu G

Abstract
Although structure-based drug design (SBDD) has become an indispensable tool in drug discovery for a long time, it continues to pose major challenges to date. With the advancement of "omics" techniques, systems biology has enriched SBDD into a new era, called polypharmacology, in which multi-targets drug or drug combination is designed to fight complex diseases. As a preliminary tool in systems biology, protein structure networks (PSNs) treat a protein as a set of residues linked by edges corresponding to the intramolecular interactions existing in folded structures between the residues. The PSN offers a computationally efficient tool to study the structure and function of proteins, and thus may facilitate structure-based drug design. Herein, we provide an overview of recent advances in PSNs, from predicting functionally important residues, to charactering protein-protein interactions and allosteric communication paths. Furthermore, we discuss potential pharmacological applications of PSN concepts and tools, and highlight the application to two families of drug targets, GPCRs and Hsp90. Although the application of PSNs as a framework for computer-aided drug discovery has been limited to date, we put forward the potential utility value in the near future and propose the PSNs could also serve as a new tool for polypharmacology research.

PMID: 27215941 [PubMed - as supplied by publisher]

[Big Biology : Supersizing Wissenschaft zu Beginn des 21. Jahrhunderts].

NTM. 2016 May 23;

Authors: Vermeulen N

PMID: 27215209 [PubMed - as supplied by publisher]