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The fungal genus Armillaria contains necrotrophic pathogens and some of the largest terrestrial organisms that cause tremendous losses in diverse ecosystems, yet how they evolved pathogenicity in a clade of dominantly non-pathogenic wood degraders remains elusive. Here we show that Armillaria species, in addition to gene duplications and de novo gene origins, acquired at least 1,025 genes via 124 horizontal gene transfer events, primarily from Ascomycota. Horizontal gene transfer might have affected plant biomass degrading and virulence abilities of Armillaria, and provides an explanation for their unusual, soft rot-like wood decay strategy. Combined multi-species expression data revealed extensive regulation of horizontally acquired and wood-decay related genes, putative virulence factors and two novel conserved pathogenicity-induced small secreted proteins, which induced necrosis in planta. Overall, this study details how evolution knitted together horizontally and vertically inherited genes in complex adaptive traits of plant biomass degradation and pathogenicity in important fungal pathogens.

IntroductionThough the nature of breastfeeding is critical, scant information is available on how the action of the milk transfer from mother to infant is regulated in humans, where the points of dysfunction are, and what can be done to optimize breastfeeding outcomes. While better therapeutic strategies are needed, before they can be devised, a basic scientific understanding of the biomechanical mechanisms that regulate human milk transfer from breast to stomach must first be identified, defined, and understood.MethodsCombining systems biology and systems medicine into a conceptual framework, using engineering design principles, this work investigates the use of biosensors to characterize human milk flow from the breast to the infant's stomach to identify points of regulation. This exploratory study used this framework to characterize Maternal/Infant Lactation physioKinetics (MILK) utilizing a Biosensor ARray (BAR) as a data collection method.ResultsParticipants tolerated the MILKBAR well during data collection. Changes in breast turgor and temperature were significant and related to the volume of milk transferred from the breast. The total milk volume transferred was evaluated in relation to contact force, oral pressure, and jaw movement. Contact force was correlated with milk flow. Oral pressure appears to be a redundant measure and reflective of jaw movements.DiscussionNipple and breast turgor, jaw movement, and swallowing were associated with the mass of milk transferred to the infant's stomach. More investigation is needed to better quantify the mass of milk transferred in relation to each variable and understand how each variable regulates milk transfer.

This study presents a novel approach for the production of cellulosic fibers from scots pine wood and their subsequent surface modification with greenly synthesized silver nanoparticles (AgNPs), leading to remarkable color effects and improved functionalities, particularly enhanced thermal stability. The size distribution of the scots pine fiber (SPF)materials was determined through sieve analysis, revealing a conversion of scots pine particles from 1.25 mm to 0.8 mm in size. The AgNPs were biosynthesized in situ on the wood fibers using the same fiber as a sustainable stabilizing and reducing agent. Scanning electron microscopy (SEM) was employed to investigate the morphologies of the control and AgNP-deposited samples, indicating a uniform distribution of nanosilver on the coated surfaces of the SPF material. The concentration of synthesized AgNPs on SPF was quantitatively measured using X-ray fluorescence (XRF) tests, ranging from 4149 ± 43 to 6329 ± 55 parts per million (PPM) depending on the AgNP concentration. The weight percentage of nanoparticles was determined by SEM-mediated energy-disruptive X-ray (EDX) analysis. Additional analyses, Fourier transform infrared spectroscopy (FTIR) test was also conducted. Thermal stability tests demonstrated an improving trend correlated with increasing nanosilver loading in the modified SPF materials. The coefficients of variation (R2) exhibited a significant relationship between nanosilver loading and most color parameters. Overall, this research presents a pioneering approach for the eco-friendly production of cellulosic fibers from scots pine wood and sustainable synthesis of AgNPs onto defibrated fibers, thus establishing a new benchmark for sustainable manufacturing processes.

Genes involved in mycoremediation were identified by comparative genomics analysis in 10 armillarioid species and selected groups of white-rot Basidiomycota (14) and soft-rot Ascomycota (12) species to confine the distinctive bioremediation capabilities of the armillarioids. The genomes were explored using phylogenetic principal component analysis (pPCA), searching for genes already documented in a biocatalysis/biodegradation database. The results underlined a distinct, increased potential of aromatics-degrading genes/enzymes in armillarioids, with particular emphasis on a high copy number and diverse spectrum of benzoate 4-monooxygenase [EC:1.14.14.92] homologs. In addition, other enzymes involved in the degradation of various monocyclic aromatics were more abundant in the armillarioids than in the other white-rot basidiomycetes, and enzymes involved in the degradation of polycyclic aromatic hydrocarbons (PAHs) were more prevailing in armillarioids and other white-rot species than in soft-rot Ascomycetes. Transcriptome profiling of A. ostoyae and A. borealis isolates confirmed that several genes involved in the degradation of benzoates and other monocyclic aromatics were distinctively expressed in the wood-invading fungal mycelia. Data were consistent with armillarioid species offering a more powerful potential in degrading aromatics. Our results provide a reliable, practical solution for screening the likely fungal candidates for their full biodegradation potential, applicability, and possible specialization based on their genomics data.

ABSTRACT Armillaria ostoyae, a species among the destructive forest pathogens from the genus Armillaria, causes root rot disease on woody plants worldwide. Efficient control measures to limit the growth and impact of this severe underground pathogen are under investigation. In a previous study, a new soilborne fungal isolate, Trichoderma atroviride SZMC 24276 (TA), exhibited high antagonistic efficacy, which suggested that it could be utilized as a biocontrol agent. The dual culture assay results indicated that the haploid A. ostoyae-derivative SZMC 23085 (AO) (C18/9) is highly susceptible to the mycelial invasion of TA. In the present study, we analyzed the transcriptome of AO and that of TA in in vitro dual culture assays to test the molecular arsenal of Trichoderma antagonism and the defense mechanisms of Armillaria. We conducted time-course analysis and functional annotation and analyzed enriched pathways and differentially expressed genes including biocontrol-related candidate genes from TA and defense-related candidate genes from AO. The results indicated that TA deployed several biocontrol mechanisms when confronted with AO. In response, AO initiated multiple defense mechanisms to protect against the fungal attack. To our knowledge, the present study offers the first transcriptome analysis of a biocontrol fungus attacking AO. Overall, this study provides insights that aid the further exploration of plant pathogen-biocontrol agent interaction mechanisms. IMPORTANCE Armillaria species can survive for decades in the soil on dead woody debris, develop rapidly under favorable conditions, and harmfully infect newly planted forests. Our previous study found Trichoderma atroviride to be highly effective in controlling Armillaria growth; therefore, our current work explored the molecular mechanisms that might play a key role in Trichoderma-Armillaria interactions. Direct confrontation assays combined with time course-based dual transcriptome analysis provided a reliable system for uncovering the interactive molecular dynamics between the fungal plant pathogen and its mycoparasitic partner. Furthermore, using a haploid Armillaria isolate allowed us to survey the deadly prey-invading activities of the mycoparasite and the ultimate defensive strategies of its prey. Our current study provides detailed insights into the essential genes and mechanisms involved in Armillaria defense against Trichoderma and the genes potentially involved in the efficiency of Trichoderma to control Armillaria. In addition, using a sensitive haploid Armillaria strain (C18/9), with its complete genome data already available, also offers the opportunity to test possible variable molecular responses of Armillaria ostoyae toward diverse Trichoderma isolates with various biocontrol abilities. Initial molecular tests of the dual interactions may soon help to develop a targeted biocontrol intervention with mycoparasites against plant pathogens.

BackgroundOxygen supplementation is commonly used to maintain oxygen saturation (SpO2) levels in preterm infants within target ranges to reduce intermittent hypoxemic (IH) events, which are associated with short- and long-term morbidities. There is not much information available about differences in oxygenation patterns in infants undergoing such supplementations nor their relation to observed IH events. This study aimed to describe oxygenation characteristics during two types of supplementation by studying SpO2 signal features and assess their performance in hypoxemia risk screening during NICU monitoring.Subjects and methodsSpO2 data from 25 infants with gestational age 0.80, F1 score > 0.60 and specificity >0.85 at observation times ≥ 1 h. Finally, we proposed a framework for risk stratification of infants using a cumulative risk score for continuous monitoring.ConclusionAnalysis of oxygen saturation signal routinely collected in the NICU, may have extensive applications in inferring subtle changes to cardiorespiratory dynamics under various conditions as well as in informing clinical decisions about infant care.

Armillarioids, including the genera Armillaria, Desarmillaria and Guyanagaster, represent white-rot specific fungal saprotrophs with soilborne pathogenic potentials on woody hosts. They propagate in the soil by root-like rhizomorphs, connecting between susceptible root sections of their hosts, and often forming extended colonies in native forests. Pathogenic abilities of Armillaria and Desarmillaria genets can readily manifest in compromised hosts, or hosts with full vigour can be invaded by virulent mycelia when exposed to a larger number of newly formed genets. Armillaria root rot-related symptoms are indicators of ecological imbalances in native forests and plantations at the rhizosphere levels, often related to abiotic environmental threats, and most likely unfavourable changes in the microbiome compositions in the interactive zone of the roots. The less-studied biotic impacts that contribute to armillarioid host infection include fungi and insects, as well as forest conditions. On the other hand, negative biotic impactors, like bacterial communities, antagonistic fungi, nematodes and plant-derived substances may find applications in the environment-friendly, biological control of armillarioid root diseases, which can be used instead of, or in combination with the classical, but frequently problematic silvicultural and chemical control measures.

Local synchronization, both prolonged and transient, of oscillatory neuronal behavior in cortical networks plays a fundamental role in many aspects of perception and cognition. Here we study networks of Hindmarsh-Rose neurons with a new type of adaptive coupling, and show that these networks naturally produce both permanent and transient synchronization of local clusters of neurons. These deterministic systems exhibit complex dynamics with 1/fη power spectra, which appears to be a consequence of a novel form of self-organized criticality.

Major depression occurs at high prevalence in the general population, often starts in juvenile years, recurs over a lifetime, and is strongly associated with disability and suicide. Searches for biological markers in depression may have been hindered by assuming that depression is a unitary and relatively homogeneous disorder, mainly of mood, rather than addressing particular, clinically crucial features or diagnostic subtypes. Many studies have implicated quantitative alterations of motility rhythms in depressed human subjects. Since a candidate feature of great public-health significance is the unusually high risk of suicidal behavior in depressive disorders, we studied correlations between a measure (vulnerability index [VI]) derived from multi-scale characteristics of daily-motility rhythms in depressed subjects (n = 36) monitored with noninvasive, wrist-worn, electronic actigraphs and their self-assessed level of suicidal thinking operationalized as a wish to die. Patient-subjects had a stable clinical diagnosis of bipolar-I, bipolar-II, or unipolar major depression (n = 12 of each type). VI was associated inversely with suicidal thinking (r = -0.61 with all subjects and r = -0.73 with bipolar disorder subjects; both p

The suprachiasmatic nucleus (SCN) is the master circadian clock in mammals and is composed of thousands of neuronal oscillators expressing different intrinsic periods. These oscillators form a coupled network with a free-running period around 24 h in constant darkness and entrainable to the external light-dark cycle (T cycle). Coupling plays an important role in setting the period of the network and its range of entrainment. Experiments in rats have shown that two subgroups of oscillators within the SCN, a ventrolateral (VL) subgroup that receives photic input and a dorsomedial (DM) subgroup that is coupled to VL, can be desynchronized under a short (22-h) T cycle, with VL entrained to the cycle and DM free-running. We use a modified Goodwin model to understand how entrainment of the subgroups to short (22-h) and long (26-h) T cycles is influenced by light intensity, the proportion of neurons that receives photic input, and coupling heterogeneity. We find that the model's critical value for the proportion of photically-sensitive neurons is in accord with actual experimental estimates, while the model's inclusion of dispersed coupling can account for the experimental observation that VL and DM desynchronize more readily under the 22-h than under the 26-h T cycle. Heterogeneous intercellular coupling within the SCN is likely central to the generation of complex behavioral patterns.

Scale invariance is a feature of complex biological systems, and abnormality of multi-scale behaviour may serve as an indicator of pathology. The hypothalamic suprachiasmatic nucleus (SCN) is a major node in central neural networks responsible for regulating multi-scale behaviour in measures of human locomotor activity. SCN also is implicated in the pathophysiology of bipolar disorder (BD) or manic-depressive illness, a severe, episodic disorder of mood, cognition and behaviour. Here, we investigated scaling behaviour in actigraphically recorded human motility data for potential indicators of BD, particularly its manic phase. A proposed index of scaling behaviour (Vulnerability Index [VI]) derived from such data distinguished between: [i] healthy subjects at high versus low risk of mood disorders; [ii] currently clinically stable BD patients versus matched controls; and [iii] among clinical states in BD patients.

While copper has essential functions as an enzymatic co-factor, excess copper ions are toxic for cells, necessitating mechanisms for regulating its levels. The cusCBFA operon of E. coli encodes a four-component efflux pump dedicated to the extrusion of Cu(I) and Ag(I) ions.We have solved the X-ray crystal structure of CusC, the outer membrane component of the Cus heavy metal efflux pump, to 2.3 Å resolution. The structure has the largest extracellular opening of any outer membrane factor (OMF) protein and suggests, for the first time, the presence of a tri-acylated N-terminal lipid anchor.The CusC protein does not have any obvious features that would make it specific for metal ions, suggesting that the narrow substrate specificity of the pump is provided by other components of the pump, most likely by the inner membrane component CusA.

Casein kinase 1 delta (CK1delta) plays a more prominent role in the regulation of circadian cycle length than its homologue casein kinase 1 epsilon (CK1epsilon) in peripheral tissues such as liver and embryonic fibroblasts. Mice lacking CK1delta die shortly after birth, so it has not been possible to assess the impact of loss of CK1delta on behavioral rhythms controlled by the master circadian oscillator in the suprachiasmatic nuclei (SCN).In the present study, mPER2::LUCIFERASE bioluminescence rhythms were monitored from SCN explants collected from neonatal mice. The data demonstrate that SCN explants from neonatal CK1delta-deficient mice oscillate, but with a longer circadian period than littermate controls. The cycle length of rhythms recorded from neonatal SCN explants of CK1epsilon-deficient mice did not differ from control explants.The results indicate that CK1delta plays a more prominent role than CK1epsilon in the maintenance of 24-hour rhythms in the master circadian oscillator.

[Display omitted] • Pulmonary hypertension (PH) complicates the clinical course and outcomes in preterm infants. • Early screening for the condition can inform medical decision and neonatal care. • Information based similarity analysis of oxygen saturation patterns identified infants with PH. • Our method using short data sets detected PH prior to diagnostic echocardiography. • Noninvasive signal-based screening can be a continuous marker of disease development. Pulmonary hypertension (PH) is a complex cardiovascular condition associated with multiple morbidities and mortality risk in preterm infants. PH often complicates the clinical course of infants who have bronchopulmonary dysplasia (BPD), a more common lung disease in these neonates, causing respiratory deterioration and an even higher risk of mortality. While risk factors and prevalence of PH are not yet well defined, early screening and management of PH in infants with BPD are recommended by consensus guidelines from the American Heart Association. In this study, we propose a screening method for PH by applying a signal analysis technique to oxygen saturation in infants. Oxygen saturation data from infant groups with BPD (41 with and 60 without PH), recorded prior to their clinical PH diagnosis were analyzed in this study. An information-based similarity approach was applied to quantify the regularity of SpO 2 fluctuations represented as binary words between adjacent five-minute segments. Similarity indices (SI) were observed to be lower in subjects with PH compared to those with BPD alone (p < 0.001). These measures were also assessed for performance in screening for PH. SI of 7-bit words, exhibited 80 % detection accuracy, 76 % sensitivity and specificity of 83 %. This index also exhibited a cross-validated mean (SD) F1-score of 0.80 (0.08) ensuring that sensitivity and recall of the screening were balanced. Similarity analysis of oxygen saturation patterns is a novel technique that can be potentially developed into a signal based early PH detection method to support clinical decision and care in this vulnerable population. [ABSTRACT FROM AUTHOR]

Objective: To test the hypothesis that environmental compared with nasal cannula oxygen decreases episodes of intermittent hypoxemia (oxygen saturations <85% for ≥10 seconds) in preterm infants on supplemental oxygen by providing a more stable hypopharyngeal oxygen concentration.Study Design: This was a single center randomized crossover trial with a 1:1 parallel allocation to order of testing. Preterm infants on supplemental oxygen via oxygen environment maintained by a servo-controlled system or nasal cannula with flow rates ≤1.0 L per kg per minute were crossed over every 24 hours for 96 hours. Data were collected electronically to capture real time numeric and waveform data from patient monitors.Results: Twenty-five infants with gestational age of 27 ± 2 weeks (mean ± SD) and a birth weight of 933 ± 328 g were studied at postnatal day 36 ± 26. The number of episodes of intermittent hypoxemia per 24 hours was 117 ± 77 (median, 98; range, 4-335) with oxygen environment vs 130 ± 63 (median, 136; range, 16-252) with nasal cannula (P = .002). Infants on oxygen environment compared with nasal cannula also had decreased episodes of severe intermittent hypoxemia (P = .005). Infants on oxygen environment compared with nasal cannula had a lower proportion of time with oxygen saturations <85% (.05 ± .03 vs .06 ± .03, P < .001), and a lower coefficient of variation of oxygen saturation (P = .02).Conclusions: In preterm infants receiving supplemental oxygen, servo-controlled oxygen environment decreases hypoxemia compared with nasal cannula.Trial Registration: ClinicalTrials.gov: NCT02794662. [ABSTRACT FROM AUTHOR]

In this paper, determination of medicinal plants was performed within eight departments in the area of the Šuma Košutnjak Natural Monument. Overall, a total of 101 medicinal plants were established in the whole research area. The identification of medicinal plants was conducted according to appropriate references. In addition to this, taxonomy analysis, definining of floral elements and finally determining of life forms for the recorded species were also performed. As for the taxonomy analysis, the greatest abundance in the whole research area was found for families Lamiaceae (12 representatives) and Rosaceae (10 representatives), while all other families are not so much present. There are overall 27 floral elements in the whole research area and among them, most of them belong to submideuropean (18 individuals) and european (16 individuals) floral elements, while the share of all other floral elements is much smaller. As for the life forms, the most dominant are hemicryptophytes (45 representatives), then phanerophytes (23 representatives) and finally therophytes (10 representatives). Differences between some departments have been established just in terms of the number of medicinal plants.

Local synchronization, both prolonged and transient, of oscillatory neuronal behavior in cortical networks plays a fundamental role in many aspects of perception and cognition. Here we study networks of Hindmarsh-Rose neurons with a new type of adaptive coupling, and show that these networks naturally produce both permanent and transient synchronization of local clusters of neurons. These deterministic systems exhibit complex dynamics with 1/fη power spectra, which appears to be a consequence of a novel form of self-organized criticality.

Nonlinear time series analysis is employed to study the complex behaviour exhibited by a coupled pair of Rossler systems. Dimensional analysis with emphasis on the topological correlation dimension and the Kolmogorov entropy of the system is carried out in the coupling parameter space. The regime of phase synchronization is identified and the extent of synchronization between the systems constituting the coupled system is quantified by the phase synchronization index. The effect of noise on the coupling between the systems is also investigated. An exhaustive study of the topological, dynamical and synchronization properties of the nonlinear system under consideration in its characteristic parameter space is attempted. [Copyright &y& Elsevier]

Major depression occurs at high prevalence in the general population, often starts in juvenile years, recurs over a lifetime, and is strongly associated with disability and suicide. Searches for biological markers in depression may have been hindered by assuming that depression is a unitary and relatively homogeneous disorder, mainly of mood, rather than addressing particular, clinically crucial features or diagnostic subtypes. Many studies have implicated quantitative alterations of motility rhythms in depressed human subjects. Since a candidate feature of great public-health significance is the unusually high risk of suicidal behavior in depressive disorders, we studied correlations between a measure (vulnerability index [VI]) derived from multi-scale characteristics of daily-motility rhythms in depressed subjects (n = 36) monitored with noninvasive, wrist-worn, electronic actigraphs and their self-assessed level of suicidal thinking operationalized as a wish to die. Patient-subjects had a stable clinical diagnosis of bipolar-I, bipolar-II, or unipolar major depression (n = 12 of each type). VI was associated inversely with suicidal thinking (r = –0.61 with all subjects and r = –0.73 with bipolar disorder subjects; both p<0.0001) and distinguished patients with bipolar versus unipolar major depression with a sensitivity of 91.7% and a specificity of 79.2%. VI may be a useful biomarker of characteristic features of major depression, contribute to differentiating bipolar and unipolar depression, and help to detect risk of suicide. An objective biomarker of suicide-risk could be advantageous when patients are unwilling or unable to share suicidal thinking with clinicians.

Scale invariance is a feature of complex biological systems, and abnormality of multi-scale behaviour may serve as an indicator of pathology. The hypothalamic suprachiasmatic nucleus (SCN) is a major node in central neural networks responsible for regulating multi-scale behaviour in measures of human locomotor activity. SCN also is implicated in the pathophysiology of bipolar disorder (BD) or manic-depressive illness, a severe, episodic disorder of mood, cognition and behaviour. Here, we investigated scaling behaviour in actigraphically recorded human motility data for potential indicators of BD, particularly its manic phase. A proposed index of scaling behaviour (Vulnerability Index [VI]) derived from such data distinguished between: [i] healthy subjects at high versus low risk of mood disorders; [ii] currently clinically stable BD patients versus matched controls; and [iii] among clinical states in BD patients.

Background: Quantitative electroencephalography (qEEG) has been suggested as a biomarker for cognitive decline in Parkinson’s disease (PD).Objective: Determine if applying a wavelet-based qEEG algorithm to 21-electrode, resting-state EEG recordings obtained in a routine clinical setting has utility for predicting cognitive impairment in PD.Methods: PD subjects, evaluated by disease stage and motor score, were compared to healthy controls (N = 20 each). PD subjects with normal (PDN, MoCA 26–30, N = 6) and impaired (PDD, MoCA ≤ 25, N = 14) cognition were compared. The wavelet-transform based time-frequency algorithm assessed the instantaneous predominant frequency (IPF) at 60 ms intervals throughout entire recordings. We then determined the relative time spent by the IPF in the four standard EEG frequency bands (RTF) at each scalp location. The resting occipital rhythm (ROR) was assessed using standard power spectral analysis.Results: Comparing PD subjects to healthy controls, mean values are decreased for ROR and RTF-Beta, greater for RTF-Theta and similar for RTF-Delta and RTF-Alpha. In logistic regression models, arithmetic combinations of RTF values [e.g., (RTF-Alpha) + (RTF-Beta)/(RTF-Delta + RTF-Theta)] and RTF-Alpha values at occipital or parietal locations are most able to discriminate between PD and controls. A principal component (PC) from principal component analysis (PCA) using RTF-band values in all subjects is associated with PD status (p = 0.004, β = 0.31, AUC = 0.780). Its loadings show positive contribution from RTF-Theta at all scalp locations, and negative contributions from RTF-Beta at occipital, parietal, central, and temporal locations. Compared to cognitively normal PD subjects, cognitively impaired PD subjects have lower median RTF-Alpha and RTF-Beta values, greater RTF-Theta values and similar RTF-Delta values. A PC from PCA using RTF-band values in PD subjects is associated with cognitive status (p = 0.002, β = 0.922, AUC = 0.89). Its loadings show positive contributions from RTF-Theta at all scalp locations, negative contributions from RTF-Beta at central locations, and negative contributions from RTF-Delta at central, frontal and temporal locations. Age, disease duration and/or sex are not significant covariates. No PC was associated with motor score or disease stage.Significance: Analyzing standard EEG recordings obtained in a community practice setting using a wavelet-based qEEG algorithm shows promise as a PD biomarker and for predicting cognitive impairment in PD.

To examine the therapeutic potential of stochastic vibrotactile stimulation (SVS) as a complementary non-pharmacological intervention for withdrawal in opioid-exposed newborns.A prospective, within-subjects single-center study was conducted in 26 opioid-exposed newborns (>37 weeks; 16 male) hospitalized since birth and treated pharmacologically for Neonatal Abstinence Syndrome. A specially-constructed mattress delivered low-level SVS (30-60Hz, 10-12μm RMS), alternated in 30-min intervals between continuous vibration (ON) and no vibration (OFF) over a 6-8 hr session. Movement activity, heart rate, respiratory rate, axillary temperature and blood-oxygen saturation were calculated separately for ON and OFF.There was a 35% reduction in movement activity with SVS (p30 sec duration for ON than OFF (p = 0.003). Incidents of tachypneic breaths and tachycardic heart beats were each significantly reduced with SVS, whereas incidents of eupneic breaths and eucardic heart beats each significantly increased with SVS (p

Many Gram-negative bacteria, including human pathogens such as Pseudomonas aeruginosa, do not have large-channel porins. This results in an outer membrane (OM) that is highly impermeable to small polar molecules, making the bacteria intrinsically resistant towards many antibiotics. In such microorganisms, the majority of small molecules are taken up by members of the OprD outer membrane protein family. Here we show that OprD channels require a carboxyl group in the substrate for efficient transport, and based on this we have renamed the family Occ, for outer membrane carboxylate channels. We further show that Occ channels can be divided into two subfamilies, based on their very different substrate specificities. Our results rationalize how certain bacteria can efficiently take up a variety of substrates under nutrient-poor conditions without compromising membrane permeability. In addition, they explain how channel inactivation in response to antibiotics can cause resistance but does not lead to decreased fitness.