Biological significance of 5S rRNA import into human mitochondria: role of ribosomal protein MRP-L18

5S rRNA is an essential component of ribosomes of all living organisms, the only known exceptions being mitochondrial ribosomes of fungi, animals, and some protists. An intriguing situation distinguishes mammalian cells: Although the mitochondrial genome contains no 5S rRNA genes, abundant import of the nuclear DNA-encoded 5S rRNA into mitochondria was reported. Neither the detailed mechanism of this pathway nor its rationale was clarified to date. In this study, we describe an elegant molecular conveyor composed of a previously identified human 5S rRNA import factor, rhodanese, and mitochondrial ribosomal protein L18, thanks to which 5S rRNA molecules can be specifically withdrawn from the cytosolic pool and redirected to mitochondria, bypassing the classic nucleolar reimport pathway. Inside mitochondria, the cytosolic 5S rRNA is shown to be associated with mitochondrial ribosomes.     

Different immunohistochemical and ultrastructural phenotypes of squamous differentiation in bladder cancer

Besides worse prognosis of bladder cancer with squamous differentiation (pure squamous cell carcinoma (SCC) or mixed urothelial carcinoma (UC/SCC)), high-grade non-keratinising squamous differentiation is difficult to identify in haematoxylin–eosin stainings. This study aims to validate routine immunohistochemical markers for squamous differentiation in a larger cohort of patients. Tissue microarrays of 89 pure SCCs and mixed UC/SCCs, 66 urothelial carcinomas (UC), precursor lesions and normal urothelium were stained for cytokeratin (CK) 5/6, CK 5/14, CK 7, CK 20 and uroplakin III. Electron microscopy was performed to confirm the differentiation. Pure SCCs displayed staining throughout the epithelium for CK 5/6 (76.6% (36/47)) and CK 5/14 (95.8% (46/48)), focal staining for CK 7 (28.9% (13/45)) and no staining for CK 20 and uroplakin III (both 0% (0/48)). UCs exhibited a basal or diffuse staining for CK 5/6 (30.2% (16/53)) and CK 5/14 (57.1% (32/56)), focal positivity for CK 7 (83.6% (46/55)), CK 20 (50.9% (29/57)) and uroplakin III (21.8% (12/55)). Each marker discriminated SCC and UC significantly (p < 0.01). A third subgroup rarely showed full epithelial staining for CK 5/6 (14.3% (1/7)) and CK 5/14 (28.6% (2/7)), focal staining for CK 7 (85.7% (6/7)) and no staining for CK 20 and uroplakin III (both 0% (0/7)). Electron microscopy could prove both, SCC and UC characteristics, revealing a transient type. A staining pattern with CK 5/6- and CK 5/14-positivity plus CK 20- and uroplakin III-negativity identified squamous differentiation in bladder tumours and revealed a third type of squamous transdifferentiation.     

Depression, anxiety, and somatoform disorders: Vague or distinct categories in primary care? Results from a large cross-sectional study

Objective

Depression, anxiety, and somatization are the most frequently observed mental disorders in primary health care. Our main objective was to draw on the often neglected general practitioners' (GPs) perspective to investigate what characterizes these three common mental diagnoses with regard to creating more suitable categories in the DSM-V and ICD-11.

Methods

We collected independent data from 1751 primary care patients (participation rate=77%) and their 32 treating GPs in Germany. Patients filled out validated patient self-report measures for depression (PHQ-9), somatic symptom severity (PHQ-15), and illness anxiety (Whiteley-7), and questions regarding coping and attribution of illness. GPs' clinical diagnoses and associated features were assessed.

Results

Patients diagnosed by their GPs with depression, anxiety, and/or somatoform disorders were significantly older, less educated, and more often female than the reference group not diagnosed with a mental disorder. They had visited the GP more often, had a longer duration of symptoms, and were more often under social or financial stress. Among the mental disorders diagnosed by the GPs, depression (OR=4.4; 95% CI=2.6 to 7.5) and comorbidity of somatoform, depressive, and anxiety disorders (OR=9.5; 95% CI=4.6 to 19.4) were associated with the largest degrees of impairment compared to the reference group. Patients diagnosed as having a somatoform/functional disorder only had mildly elevated impairment on all dimensions (OR=2.0; 95% CI=1.4 to 2.7). Similar results were found for the physicians' attribution of psychosocial factors for cause and maintenance of the disease, difficult patient-doctor relationship, and self-assessed mental disorder.

Conclusion

In order to make the DSM-V and ICD-11 more suitable for primary care, we propose providing appropriate diagnostic categories for (1) the many mild forms of mental syndromes typically seen in primary care; and (2) the severe forms of comorbidity between somatoform, depressive, and/or anxiety disorder, e.g., with a dimensional approach.     

Motor excitability during imagination and observation of foot dorsiflexions

To explore the effects of motor imagery (MI) and action observation (AO) of foot movements on motor excitability. Fifteen healthy subjects were studied at rest, during MI of foot dorsiflexions and during watching a video of foot dorsiflexions. Transcranial magnetic stimulation was used to explore corticospinal and intracortical excitability by comparing amplitudes of motor-evoked potentials during the different conditions. F waves were recorded to test the spinal motoneuronal excitability. MI and AO increased corticospinal excitability, but MI was more effective than AO. During MI, intracortical inhibition was reduced. Intracortical facilitation and spinal motoneuronal excitability remained unchanged. Excitability increases were similar for the right and the left leg when recording from the side the subjects had focused their MI on. However, MI of left foot dorsiflexions did not increase excitability in the right tibial anterior muscle. MI and AO of foot dorsiflexions enhance motor excitability. MI induced a disinhibition in the motor cortex. The lack of excitability increase during MI of contralateral foot movements might be related to the alternating movement pattern during walking. MI and AO effects could support the restitution of motor deficits in neurological diseases with impaired motor excitability.     

The Relationship Between Life Satisfaction and Health Behavior: A Cross-cultural Analysis of Young Adults

Background  

Positive well-being has been associated with a range of favorable health outcomes. The contribution of health-promoting behaviors is unclear.