Front Genet. 2012; 3: 1
Shriner D

Association studies are a staple of genotype-phenotype mapping studies, whether they are based on single markers, haplotypes, candidate genes, genome-wide genotypes, or whole genome sequences. Although genetic epidemiological studies typically contain data collected on multiple traits which themselves are often correlated, most analyses have been performed on single traits. Here, I review several methods that have been developed to perform multiple trait analysis. These methods range from traditional multivariate models for systems of equations to recently developed graphical approaches based on network theory. The application of network theory to genetics is termed systems genetics and has the potential to address long-standing questions in genetics about complex processes such as coordinate regulation, homeostasis, and pleiotropy.

Front Genet. 2011; 2: 98
Pallet N, Thervet E, Desjardins M

Oligonucleotide microarray technology has created a small revolution in the transplant community because it has helped to decipher previously unknown molecular processes involved in allograft pathology, redefined molecular patterns of diseases that are indistinguishable at the pathological level and made possible the definition of new prognostic factors for long-term graft outcomes. However, given the tremendous complexity of the biological processes that are involved in the pathology of a transplanted organ, the interpretation of transcriptomic data can be speculative and oversimplified. Here, we discuss critical considerations regarding the nature of the object studied by cDNA microarray technology, the means by which it is observed, the interpretation of the observations, and whether the observations make sense in the context of transplant-related scientific questions. Given these limitations, we believe that global approaches based on more functional biological intermediates are necessary for a better understanding of the molecular processes that regulate the physiopathology of the transplanted organ.

Front Genet. 2011; 2: 88
Clifford H, Wessely F, Pendurthi S, Emes RD

The use of genome-wide methylation arrays has proved very informative to investigate both clinical and biological questions in human epigenomics. The use of clustering methods either for exploration of these data or to compare to an a priori grouping, e.g., normal versus disease allows assessment of groupings of data without user bias. However no consensus on the methods to use for clustering of methylation array approaches has been reached. To determine the most appropriate clustering method for analysis of illumina array methylation data, a collection of data sets was simulated and used to compare clustering methods. Both hierarchical clustering and non-hierarchical clustering methods (k-means, k-medoids, and fuzzy clustering algorithms) were compared using a range of distance and linkage methods. As no single method consistently outperformed others across different simulations, we propose a method to capture the best clustering outcome based on an additional measure, the silhouette width. This approach produced a consistently higher cluster accuracy compared to using any one method in isolation.

Front Genet. 2011; 2: 81
Amen MA, Griffiths A

The herpesviruses are a family of large DNA viruses capable of establishing lifelong infections. Recent reports have shown that herpesviruses package non-coding RNA into virions; this follows earlier observations showing that coding RNAs are detected in virions. Packaging RNAs allows for their function immediately after virus entry and in the absence of de novo transcription. Despite the collective understanding that RNAs are packaged into herpesvirus virions, many questions remain. This review will highlight what is known regarding packaged coding and non-coding RNAs and discuss their potential impact to virus biology.

Zookeys. 2011; 33-44
Gómez-Zurita J

The study of external morphology of the New Caledonian leaf beetle Dematochroma foaensis Jolivet, Verma & Mille (Chrysomelidae, Eumolpinae, Colaspoidini) substantiates its new combination into the genus Rhyparida Baly (Chrysomelidae, Eumolpinae, Nodinini). The species is redescribed here to highlight characters important for suprageneric diagnosis. This is the second species of Nodinini found in New Caledonia, otherwise rich in species of Colaspoidini, raising questions about the paucity of Rhyparida and this tribe in New Caledonian fauna, when they are dominant in surrounding archipelagoes, and very rich in potential source areas such as Australia and New Guinea. Some alternative explanations for this pattern are advanced, serving as alternative hypotheses until our knowledge on the ecology of these species improves or supported phylogenetic scenarios become available for this group.

J Biol Chem. 2012 Feb 2;
Kurokawa K, Ryu KH, Ichikawa R, Matsuda A, Kim MS, Lee H, Chae JH, Shimizu T, Saitoh T, Kuwano K, Akira S, Dohmae N, Nakayama H, Lee BL

Bacterial lipoproteins/lipopeptides inducing host innate immune responses are sensed by mammalian toll-like receptor 2 (TLR2). These bacterial lipoproteins are structurally divided into two groups, diacylated or triacylated lipoproteins, by the absence or presence of an amide-linked fatty acid. The presence of diacylated lipoproteins has been predicted in low-GC content Gram-positive bacteria and mycoplasmas based on the absence of one modification enzyme in their genomes; however, we recently determined triacylated structures in low-GC Gram-positive Staphylococcus aureus, raising questions about the actual lipoprotein structure in other low-GC content Gram-positive bacteria. Here, through intensive MS analyses, we identified a novel and unique bacterial lipoprotein structure containing an N-acyl-S-monoacyl-glyceryl-cysteine (named the lyso structure) from low-GC Gram-positive Enterococcus faecalis, Bacillus cereus, Streptococcus sanguinis, and Lactobacillus bulgaricus. Two of the purified native lyso-form lipoproteins induced pro-inflammatory cytokine production from mice macrophages in a TLR2-dependent and TLR1-independent manner but with a different dependence on TLR6. Additionally, two other new lipoprotein structures were identified. One is the N-acetyl lipoprotein structure containing N-acetyl-S-diacyl-glyceryl-cysteine, which was found in five Gram-positive bacteria, including Bacillus subtilis. The N-acetyl lipoproteins induced the pro-inflammatory cytokines through the TLR-2/6 heterodimer. The other was identified in a mycoplasma strain and is an unusual diacyl lipoprotein structure containing two amino acids before the lipid-modified cysteine residue. Taken together, our results suggest the existence of novel TLR2-stimulating lyso- and N-acetyl-forms of lipoproteins that are conserved in low-GC content Gram-positive bacteria and provide clear evidence for the presence of yet-to-be identified key enzymes involved in the bacterial lipoprotein biosynthesis.

Genes Dev. 2012 Feb 1; 26(3): 203-34
Hayden MS, Ghosh S

The ability to sense and adjust to the environment is crucial to life. For multicellular organisms, the ability to respond to external changes is essential not only for survival but also for normal development and physiology. Although signaling events can directly modify cellular function, typically signaling acts to alter transcriptional responses to generate both transient and sustained changes. Rapid, but transient, changes in gene expression are mediated by inducible transcription factors such as NF-κB. For the past 25 years, NF-κB has served as a paradigm for inducible transcription factors and has provided numerous insights into how signaling events influence gene expression and physiology. Since its discovery as a regulator of expression of the κ light chain gene in B cells, research on NF-κB continues to yield new insights into fundamental cellular processes. Advances in understanding the mechanisms that regulate NF-κB have been accompanied by progress in elucidating the biological significance of this transcription factor in various physiological processes. NF-κB likely plays the most prominent role in the development and function of the immune system and, not surprisingly, when dysregulated, contributes to the pathophysiology of inflammatory disease. As our appreciation of the fundamental role of inflammation in disease pathogenesis has increased, so too has the importance of NF-κB as a key regulatory molecule gained progressively greater significance. However, despite the tremendous progress that has been made in understanding the regulation of NF-κB, there is much that remains to be understood. In this review, we highlight both the progress that has been made and the fundamental questions that remain unanswered after 25 years of study.

Menopause Int. 2012 Feb 2;
Alidoosti K, Abbaszadeh A, Hosseininasab A

Menopause is defined as amenorrhea for one year. Signs and symptoms are categorized as physical and psychological changes, including depression, hot flushes and ageing. Woman's responses to menopause are governed by lifestyle factors. The purpose of this study was to determine how Iranian women experience menopause and hormone therapy. A qualitative inquiry was conducted through semistructured, in-depth interviews to explore study questions in 11 menopausal women. Participants had positive and negative menopause experiences. Negative menopause experiences are due to severity of symptoms. Menopause can be facilitated by increasing women's knowledge about this phase and ways to cope with it.

Circ Res. 2012 Feb 3; 110(3): 496-507
van Rooij E, Purcell AL, Levin AA

Rarely a new research area has gotten such an overwhelming amount of attention as have microRNAs. Although several basic questions regarding their biological principles still remain to be answered, many specific characteristics of microRNAs in combination with compelling therapeutic efficacy data and a clear involvement in human disease have triggered the biotechnology community to start exploring the possibilities of viewing microRNAs as therapeutic entities. This review serves to provide some general insight into some of the current microRNAs targets, how one goes from the initial bench discovery to actually developing a therapeutically useful modality, and will briefly summarize the current patent landscape and the companies that have started to explore microRNAs as the next drug target.

Clin Orthop Relat Res. 2012 Feb 1;
Malek F, Somerson JS, Mitchel S, Williams RP

INTRODUCTION: Patients with aggressive lower extremity musculoskeletal tumors may be candidates for either above-knee amputation or limb-salvage surgery. However, the subjective and objective benefits of limb-salvage surgery compared with amputation are not fully clear. QUESTIONS/PURPOSES: We therefore compared functional status and quality of life for patients treated with above-knee amputation versus limb-salvage surgery. METHODS: We reviewed 20 of 51 patients aged 15 years and older treated with above-knee amputation or limb-salvage surgery for aggressive musculoskeletal tumors around the knee between 1994 and 2004 as a retrospective cohort study. At last followup we obtained the Physiological Cost Index, the Reintegration to Normal Living Index, SF-36, and the Toronto Extremity Salvage Score questionnaires. The minimum followup was 12 months (median, 56 months; range, 12-108 months). RESULTS: Compared with patients having above-knee amputation, patients undergoing limb-salvage surgery had superior Physiological Cost Index scores and Reintegration to Normal Living Index. The Toronto Extremity Salvage scores and SF-36 scores were similar in the two groups. CONCLUSION: These data suggest that limb-salvage surgery offers better gait efficiency and return to normal living compared with above-knee amputation, but does not improve the patient's perception of quality of life. LEVEL OF EVIDENCE: Level III, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Clin Orthop Relat Res. 2012 Feb 1;
Ito Y, Matsushita I, Watanabe H, Kimura T

BACKGROUND: The direct anterior approach in THA requires no detachment of muscle insertions. However, damage to the short external rotator muscles may occur when attempting to elevate the femur for exposure. Although the anatomic insertions of these muscles are approximately known, there are no quantitative data regarding their locations. QUESTIONS/PURPOSES: We therefore asked where and how the tendons attach to the inner aspect of the greater trochanter. METHODS: In 20 cadaveric hips we identified the attachments of the short external rotator tendons on the medial aspect of the greater trochanter. Mapping of the attachment site was performed by defining coordinate axes; the total width and height of the greater trochanter represented 100% and distances of the attachment from the anteroinferior reference point were given. RESULTS: The mean anterior border location of the conjoined tendon (obturator internus, gemellus superior, and gemellus inferior) attachment was located at 29% (13 mm from the anteroinferior reference point), its posterior border at 53% (23 mm), its mean superior border at 70% (15 mm), and its mean inferior border at 24% (5 mm). The mean anterior border of the piriformis tendon attachment was located at 57% (25 mm), its mean posterior border at 78% (34 mm), its mean superior border at 64% (17 mm), and its inferior border at 55% (12 mm). There was considerable variation in these attachment sites among individuals. CONCLUSIONS: The insertion of the conjoined tendon extends to the anterosuperior aspect of the greater trochanter. Together with the considerable variation of the attachment site, external rotator muscles remain at risk of being damaged during the capsular release.

Indian J Pediatr. 2012 Feb 3;
Choudhary MG, Jain A, Chahar CK, Singhal AK

OBJECTIVE: To asses the prevalence of learning disorders in school going children and to compare the socio-demographic variables and other related factors with learning disorder. METHODS: All the 500 students of class III to V with all sections were given the dyslexia assessment questionnaire (DAQ) to fill; 468 students returned the completed forms.Statistical analysis was done using chi-square test. Only 68 children scored ≥4 on DAQ were given MISIC (Mallin's intelligence scale for Indian children) for IQ assessment and DST-J for dyslexia screening. Forty-eight students were labeled as dyslexia and further diagnosis was confirmed by DSM IV- TR classification. RESULTS: Prevalence of learning disorders (LD) was found to be 10.25% with higher in males than females (11.40% vs. 7.14%).The delivery complications (20.83% vs. 4.17%; X (2)-4.667, p value-0.031) were more in LD and more family members were left handed (16.67% vs. 2.08%; X (2)-4.41, p value-0.036) as compared to control group. In classroom behavior, children with LD asked questions less (10.42% vs. 75%; X (2)-40.91, p value-0.0001), answered questions less frequently (6.25% vs. 79.16%; X (2)-52.15, p value-0.0001) and took notes less attentively than control group (4.17% vs. 58.33%; X (2)-32.77, p value-0.0001). CONCLUSIONS: The current study, therefore, is an attempt to identify children with learning disorders and explore the prevalence of the problem and etiological factors e.g., family environment, social factors and developmental issues of child and associated co-morbidities. More studies with larger sample size should be undertaken to get accurate picture of these disorders.There is also need for some community based programme to raise the level of awareness and knowledge about these disorders in general population.