SOS genes are rapidly induced while translesion synthesis polymerase activity is temporally regulated.

The DNA damage inducible SOS response in bacteria serves to increase survival of the species at the cost of mutagenesis. The SOS response first initiates error-free repair followed by error-prone repair. Here, we have employed a multi-omics approach to elucidate the temporal coordination of the SOS response.

Activation of multiple stress responses in substantially lowers the minimal inhibitory concentration when combining two novel antibiotic drug candidates.

The past few decades have been plagued by an increasing number of infections caused by antibiotic resistant bacteria. To mitigate the rise in untreatable infections, we need new antibiotics with novel targets and drug combinations that reduce resistance development. The novel β-clamp targeting antimicrobial peptide BTP-001 was recently shown to have a strong additive effect in combination with the halogenated pyrrolopyrimidine JK-274.

Halogenated Pyrrolopyrimidines with Low MIC on and Synergistic Effects with an Antimicrobial Peptide.

Currently, there is a world-wide rise in antibiotic resistance causing burdens to individuals and public healthcare systems. At the same time drug development is lagging behind. Therefore, finding new ways of treating bacterial infections either by identifying new agents or combinations of drugs is of utmost importance.

Refining the phenotype associated with GNB1 mutations: Clinical data on 18 newly identified patients and review of the literature.

De novo germline mutations in GNB1 have been associated with a neurodevelopmental phenotype. To date, 28 patients with variants classified as pathogenic have been reported. We add 18 patients with de novo mutations to this cohort, including a patient with mosaicism for a GNB1 mutation who presented with a milder phenotype.

Recessive mutations in ATP8A2 cause severe hypotonia, cognitive impairment, hyperkinetic movement disorders and progressive optic atrophy.

Background: ATP8A2 mutations have recently been described in several patients with severe, early-onset hypotonia and cognitive impairment. The aim of our study was to characterize the clinical phenotype of patients with ATP8A2 mutations.

Methods: An observational study was conducted at multiple diagnostic centres.

Genetic counseling in industry settings: Opportunities in the era of precision health.

The skill sets of genetic counselors are strongly utilized in industry, as evidenced by 20% of genetic counselors reporting employment within industry in 2016. In addition, industry genetic counselors are expanding their roles, taking on new responsibilities, and creating new opportunities. These advances have impacted the profession as a whole including, but not limited to, genetic counseling training curricula, a shift back to genetic counseling directly to patients, and a growing influence of genetic counselors on industry test offerings.

Informed choice in direct-to-consumer genetic testing (DTCGT) websites: a content analysis of benefits, risks, and limitations.

An informed choice about health-related direct-to-consumer genetic testing (DTCGT) requires knowledge of potential benefits, risks, and limitations. To understand the information that potential consumers of DTCGT services are exposed to on company websites, we conducted a content analysis of 23 health-related DTCGT websites. Results revealed that benefit statements outweighed risk and limitation statements 6 to 1.

Analysis of SCA-2 and SCA-3 repeats in Parkinsonism: evidence of SCA-2 expansion in a family with autosomal dominant Parkinson's disease.

The spinocerebellar ataxias (SCAs) are progressive neurodegenerative disorders linked to more than 20 genetic loci. Most often, these diseases are caused by expansion of triplet repeats encoding polyglutamine (polyQ) tracts. The phenotype is variable and can cause a disease that overlaps clinically with Parkinson's disease (PD).

Analysis of familial and sporadic restless legs syndrome in age of onset, gender, and severity features.

Restless Legs Syndrome is characterized by the irresistible, often indescribable unpleasant urge to move the limbs while resting. It has an estimated prevalence of approximately 29.3 % in US private practice.

Smell testing is abnormal in 'lubag' or X-linked dystonia-parkinsonism: a pilot study.

We administered a culturally corrected University of Pennsylvania Smell Identification Test (ccUPSIT) consisting of 25 odor items to 20 patients with 'Lubag' or X-linked dystonia-parkinsonism and 20 control subjects matched by sex, age, educational background, smoking history, and geographical origin. The mean ccUPSIT score of Lubag patients (18 +/- 3.19) was statistically lower (P = 0.

Profile of families with parkinsonism-predominant spinocerebellar ataxia type 2 (SCA2).

Spinocerebellar ataxia type 2 (SCA2) has been recognized recently as an uncommon cause of parkinsonism, an alternate presentation to the typical cerebellar disorder. This research review summarizes the existing literature on parkinsonism-predominant presentation SCA2 and presents new clinical cases of patients with this condition. Various phenotypes are noted in this subtype of SCA2, including parkinsonism indistinguishable from idiopathic Parkinson's disease (PD), parkinsonism plus ataxia, motor neuron disease, and postural tremor.

Exercise-induced dystonia as a preceding symptom of familial Parkinson's disease.

Paroxysmal exercise-induced dystonia can occur with Parkinson's disease (PD), and in rare cases, this can also be the presenting symptom. We report on 2 second cousins (no known consanguinity) who presented with paroxysmal exercise-induced dystonia who later developed clinical features of PD. Although autosomal recessive inheritance was suggested, and the dystonic features further suggest parkin as a possible cause, sequencing for parkin mutations was negative and this family may represent a genetic variant of PD.

Association between cardiac denervation and parkinsonism caused by alpha-synuclein gene triplication.

Parkinson's disease patients frequently have symptoms and signs of autonomic nervous dysfunction that are the source of considerable disability. Recent studies have revealed that most patients with Parkinson's disease, and all with Parkinson's disease-associated orthostatic hypotension, have a loss of cardiac sympathetic innervation. Familial Parkinson's disease, caused by mutation of the gene encoding alpha-synuclein, also features orthostatic hypotension, sympathetic neurocirculatory failure and cardiac sympathetic denervation.

Early-onset Parkinson's disease caused by a compound heterozygous DJ-1 mutation.

Mutations in DJ-1 have been linked to an autosomal recessive form of early-onset parkinsonism. To identify mutations causing Parkinson's disease (PD), we sequenced exons 1 through 7 of DJ-1 in 107 early-onset (age at diagnosis up to 50 years) PD subjects. One subject had a frameshift mutation in the first coding exon and an exon 7 splice mutation both predicted to result in a loss of functional protein.

Mutation at the SCA17 locus is not a common cause of parkinsonism.

Spinocerebellar ataxia (SCA) 17 is a dominant, progressive, neurodegenerative disorder. The disease is caused by a triplet repeat expansion mutation within TATA-binding protein (TBP). Ataxia, dementia, parkinsonism and dystonia are common features.

Primary hyperhidrosis--evidence for autosomal dominant inheritance.

Primary hyperhidrosis is a neurogenic disorder of unknown cause characterized by excessive sweating in the palmar surface of the hands, armpits, groin and feet. In the course of a therapeutic trial for primary hyperhidrosis, 62 % of patients reported a positive family history. Examination of these pedigrees demonstrated a sibling recurrence risk of lambdas = 29-48 and an offspring recurrence risk of lambdao = 41-68 indicating that hyperhidrosis can be an inherited condition.

SCA2 may present as levodopa-responsive parkinsonism.

Some kindreds with familial parkinsonism exhibit genetic anticipation, suggesting possible involvement of trinucleotide repeat expansion. Recent reports have shown trinucleotide repeat expansions in the spinocerebellar ataxia 2 (SCA2) gene in patients with levodopa-responsive parkinsonism. We tested 136 unrelated patients with familial parkinsonism for SCA2 mutations.

Familial Lewy body diseases.

Lewy body disease includes clinically and pathologically defined disorders in which Lewy bodies occur in the nervous system. In recent years, the molecular features of these disorders have been emerging. Several genetic loci have been identified in association with familial Lewy body disease; however, the genetic risks underlying most cases of familial Lewy body disease remain to be discovered.